Electrode structures and methods for their use in cardiovascular reflex control

ABSTRACT

Devices, systems and methods are described by which the blood pressure, nervous system activity, and neurohormonal activity may be selectively and controllably reduced by activating baroreceptors. A baroreceptor activation device is positioned near a baroreceptor, preferably a baroreceptor located in the carotid sinus. A control system may be used to modulate the baroreceptor activation device. The control system may utilize an algorithm defining a stimulus regimen which promotes long term efficacy and reduces power requirements/consumption. The baroreceptor activation device may utilize electrodes to activate the baroreceptors. The electrodes may be adapted for connection to the carotid arteries at or near the carotid sinus, and may be designed to minimize extraneous tissue stimulation.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/300,232, filed Nov. 18, 2011, which is a continuation of U.S. patentapplication Ser. No. 12/762,891, filed Apr. 19, 2010, which is acontinuation of U.S. patent application Ser. No. 11/535,666, filed Sep.27, 2006, which is a continuation of U.S. patent application Ser. No.10/402,911, filed on Mar. 27, 2003, now issued as U.S. Pat. No.7,499,742, which: (1) is a continuation-in-part of U.S. patentapplication Ser. No. 09/963,777, filed on Sep. 26, 2001, now issued asU.S. Pat. No. 7,158,832, which is a continuation-in-part of U.S. patentapplication Ser. No. 09/671,850, filed on Sep. 27, 2000, now issued asU.S. Pat. No. 6,522,926; and (2) claims the benefit of U.S. ProvisionalApplication No. 60/368,222, filed on Mar. 27, 2002. The full disclosuresof each of these applications are incorporated herein by reference.

BACKGROUND OF THE INVENTION

The present invention generally relates to medical devices and methodsof use for the treatment and/or management of cardiovascular and renaldisorders. Specifically, the present invention relates to devices andmethods for controlling the baroreflex system for the treatment and/ormanagement of cardiovascular and renal disorders and their underlyingcauses and conditions.

Cardiovascular disease is a major contributor to patient illness andmortality. It also is a primary driver of health care expenditure,costing more than $326 billion each year in the United States.Hypertension, or high blood pressure, is a major cardiovascular disorderthat is estimated to affect over 50 million people in the United Satesalone. Of those with hypertension, it is reported that fewer than 30%have their blood pressure under control. Hypertension is a leading causeof heart failure and stroke. It is the primary cause of death in over42,000 patients per year and is listed as a primary or contributingcause of death in over 200,000 patients per year in the U.S.Accordingly, hypertension is a serious health problem demandingsignificant research and development for the treatment thereof.

Hypertension occurs when the body's smaller blood vessels (arterioles)constrict, causing an increase in blood pressure. Because the bloodvessels constrict, the heart must work harder to maintain blood flow atthe higher pressures. Although the body may tolerate short periods ofincreased blood pressure, sustained hypertension may eventually resultin damage to multiple body organs, including the kidneys, brain, eyesand other tissues, causing a variety of maladies associated therewith.The elevated blood pressure may also damage the lining of the bloodvessels, accelerating the process of atherosclerosis and increasing thelikelihood that a blood clot may develop. This could lead to a heartattack and/or stroke. Sustained high blood pressure may eventuallyresult in an enlarged and damaged heart (hypertrophy), which may lead toheart failure.

Heart failure is the final common expression of a variety ofcardiovascular disorders, including ischemic heart disease. It ischaracterized by an inability of the heart to pump enough blood to meetthe body's needs and results in fatigue, reduced exercise capacity andpoor survival. It is estimated that approximately 5,000,000 people inthe United States suffer from heart failure, directly leading to 39,000deaths per year and contributing to another 225,000 deaths per year. Itis also estimated that greater than 400,000 new cases of heart failureare diagnosed each year. Heart failure accounts for over 900,000hospital admissions annually, and is the most common discharge diagnosisin patients over the age of 65 years. It has been reported that the costof treating heart failure in the United States exceeds $20 billionannually. Accordingly, heart failure is also a serious health problemdemanding significant research and development for the treatment and/ormanagement thereof.

Heart failure results in the activation of a number of body systems tocompensate for the heart's inability to pump sufficient blood. Many ofthese responses are mediated by an increase in the level of activationof the sympathetic nervous system, as well as by activation of multipleother neurohormonal responses. Generally speaking, this sympatheticnervous system activation signals the heart to increase heart rate andforce of contraction to increase the cardiac output; it signals thekidneys to expand the blood volume by retaining sodium and water; and itsignals the arterioles to constrict to elevate the blood pressure. Thecardiac, renal and vascular responses increase the workload of theheart, further accelerating myocardial damage and exacerbating the heartfailure state. Accordingly, it is desirable to reduce the level ofsympathetic nervous system activation in order to stop or at leastminimize this vicious cycle and thereby treat or manage the heartfailure.

A number of drug treatments have been proposed for the management ofhypertension, heart failure and other cardiovascular disorders. Theseinclude vasodilators to reduce the blood pressure and ease the workloadof the heart, diuretics to reduce fluid overload, inhibitors andblocking agents of the body's neurohormonal responses, and othermedicaments.

Various surgical procedures have also been proposed for these maladies.For example, heart transplantation has been proposed for patients whosuffer from severe, refractory heart failure. Alternatively, animplantable medical device such as a ventricular assist device (VAD) maybe implanted in the chest to increase the pumping action of the heart.Alternatively, an intra-aortic balloon pump (IABP) may be used formaintaining heart function for short periods of time, but typically nolonger than one month. Other surgical procedures are available as well.

It has been known for decades that the wall of the carotid sinus, astructure at the bifurcation of the common carotid arteries, containsstretch receptors (baroreceptors) that are sensitive to the bloodpressure. These receptors send signals via the carotid sinus nerve tothe brain, which in turn regulates the cardiovascular system to maintainnormal blood pressure (the baroreflex), in part through activation ofthe sympathetic nervous system. Electrical stimulation of the carotidsinus nerve (baropacing) has previously been proposed to reduce bloodpressure and the workload of the heart in the treatment of high bloodpressure and angina. For example, U.S. Pat. No. 6,073,048 to Kieval etal. discloses a baroreflex modulation system and method for stimulatingthe baroreflex arc based on various cardiovascular and pulmonaryparameters.

Although each of these alternative approaches is beneficial in someways, each of the therapies has its own disadvantages. For example, drugtherapy is often incompletely effective. Some patients may beunresponsive (refractory) to medical therapy. Drugs often have unwantedside effects and may need to be given in complex regimens. These andother factors contribute to poor patient compliance with medicaltherapy. Drug therapy may also be expensive, adding to the health carecosts associated with these disorders. Likewise, surgical approaches arevery costly, may be associated with significant patient morbidity andmortality and may not alter the natural history of the disease.Baropacing also has not gained acceptance. Several problems withelectrical carotid sinus nerve stimulation have been reported in themedical literature. These include the invasiveness of the surgicalprocedure to implant the nerve electrodes, and postoperative pain in thejaw, throat, face and head during stimulation. In addition, it has beennoted that high voltages sometimes required for nerve stimulation maydamage the carotid sinus nerves. Accordingly, there continues to be asubstantial and long felt need for new devices and methods for treatingand/or managing high blood pressure, heart failure and their associatedcardiovascular and nervous system disorders.

U.S. Pat. No. 6,522,926, signed to the Assignee of the presentapplication, describes a number of systems and methods intended toactivate baroreceptors in the carotid sinus and elsewhere in order toinduce the baroreflex. Numerous specific approaches are described,including the use of coil electrodes placed over the exterior of thecarotid sinus near the carotid bifurcation. While such electrode designsoffer substantial promise, there is room for improvement in a number ofspecific design areas. For example, it would be desirable to providedesigns which permit electrode structures to be closely and conformablysecured over the exterior of a carotid sinus or other blood vessels sothat efficient activation of the underlying baroreceptors can beachieved. It would be further desirable to provide specific electrodestructures which can be variably positioned at different locations overthe carotid sinus wall or elsewhere. At least some of these objectiveswill be met by these inventions described herein below.

BRIEF SUMMARY OF THE INVENTION

To address hypertension, heart failure and their associatedcardiovascular and nervous system disorders, the present inventionprovides a number of devices, systems and methods by which the bloodpressure, nervous system activity, and neurohormonal activity may beselectively and controllably regulated by activating baroreceptors. Byselectively and controllably activating baroreceptors, the presentinvention reduces excessive blood pressure, sympathetic nervous systemactivation and neurohormonal activation, thereby minimizing theirdeleterious effects on the heart, vasculature and other organs andtissues.

The present invention provides systems and methods for treating apatient by inducing a baroreceptor signal to effect a change in thebaroreflex system (e.g., reduced heart rate, reduced blood pressure,etc.). The baroreceptor signal is activated or otherwise modified byselectively activating baroreceptors. To accomplish this, the system andmethod of the present invention utilize a baroreceptor activation devicepositioned near a baroreceptor in the carotid sinus, aortic arch, heart,common carotid arteries, subclavian arteries, and/or brachiocephalicartery. Preferably, the baroreceptor activation device is located in theright and/or left carotid sinus (near the bifurcation of the commoncarotid artery) and/or the aortic arch. By way of example, notlimitation, the present invention is described with reference to thecarotid sinus location.

Generally speaking, the baroreceptor activation device may be activated,deactivated or otherwise modulated to activate one or more baroreceptorsand induce a baroreceptor signal or a change in the baroreceptor signalto thereby effect a change in the baroreflex system. The baroreceptoractivation device may be activated, deactivated, or otherwise modulatedcontinuously, periodically, or episodically. The baroreceptor activationdevice may comprise a wide variety of devices which utilize electrodesto directly or indirectly activate the baroreceptor.

The baroreceptor may be activated directly, or activated indirectly viathe adjacent vascular tissue. The baroreceptor activation device will bepositioned outside the vascular wall. To maximize therapeutic efficacy,mapping methods may be employed to precisely locate or position thebaroreceptor activation device.

The present invention is directed particularly at electrical means andmethods to activate baroreceptors, and various electrode designs areprovided. The electrode designs may be particularly suitable forconnection to the carotid arteries at or near the carotid sinus, and maybe designed to minimize extraneous tissue stimulation. While beingparticularly suitable for use on the carotid arteries at or near thecarotid sinus, the electrode structures and assemblies of the presentinvention will also find use for external placement and securement ofelectrodes about other arteries, and in some cases veins, havingbaroreceptor and other electrically activated receptors therein.

In a first aspect of the present invention, a baroreceptor activationdevice or other electrode useful for a carotid sinus or other bloodvessel comprises a base having one or more electrodes connected to thebase. The base has a length sufficient to extend around at least asubstantial portion of the circumference of a blood vessel, usually anartery, more usually a carotid artery at or near the carotid sinus. By“substantial portion,” it is meant that the base will extend over atleast 25% of the vessel circumference, usually at least 50%, moreusually at least 66%, and often at least 75% or over the entirecircumference. Usually, the base is sufficiently elastic to conform tosaid circumference or portion thereof when placed therearound. Theelectrode connected to the base is oriented at least partly in thecircumferential direction and is sufficiently stretchable to bothconform to the shape of the carotid sinus when the base is conformedthereover and accommodate changes in the shape and size of the sinus asthey vary over time with heart pulse and other factors, including bodymovement which causes the blood vessel circumference to change.

Usually, at least two electrodes will be positioned circumferentiallyand adjacent to each other on the base. The electrode(s) may extend overthe entire length of the base, but in some cases will extend over lessthan 75% of the circumferential length of the base, often being lessthan 50% of the circumferential length, and sometimes less than 25% ofthe circumferential length. Thus, the electrode structures may coverfrom a small portion up to the entire circumferential length of thecarotid artery or other blood vessel. Usually, the circumferentiallength of the elongate electrodes will cover at least 10% of thecircumference of the blood vessel, typically being at least 25%, oftenat least 50%, 75%, or the entire length. The base will usually havefirst and second ends, wherein the ends are adapted to be joined, andwill have sufficient structural integrity to grasp the carotid sinus.

In a further aspect of the present invention, an extravascular electrodeassembly comprises an elastic base and a stretchable electrode. Theelastic base is adapted to be conformably attached over the outside of atarget blood vessel, such as a carotid artery at or near the carotidsinus, and the stretchable electrode is secured over the elastic baseand capable of expanding and contracting together with the base. In thisway, the electrode assembly is conformable to the exterior of thecarotid sinus or other blood vessel. Preferably, the elastic base isplanar, typically comprising an elastomeric sheet. While the sheet maybe reinforced, the reinforcement will be arranged so that the sheetremains elastic and stretchable, at least in the circumferentialdirection, so that the base and electrode assembly may be placed andconformed over the exterior of the blood vessel. Suitable elastomericsheets may be composed of silicone, latex, and the like.

To assist in mounting the extravascular electrode over the carotid sinusor other blood vessel, the assembly will usually include two or moreattachment tabs extending from the elastomeric sheet at locations whichallow the tabs to overlap the elastic base and/or be directly attachedto the blood vessel wall when the base is wrapped around or otherwisesecured over a blood vessel. In this way, the tabs may be fastened tosecure the backing over the blood vessel.

Preferred stretchable electrodes comprise elongated coils, where thecoils may stretch and shorten in a spring-like manner. In particularlypreferred embodiments, the elongated coils will be flattened over atleast a portion of their lengths, where the flattened portion isoriented in parallel to the elastic base. The flattened coil providesimproved electrical contact when placed against the exterior of thecarotid sinus or other blood vessel.

In a further aspect of the present invention, an extravascular electrodeassembly comprises a base and an electrode structure. The base isadapted to be attached over the outside of a carotid artery or otherblood vessel and has an electrode-carrying surface formed over at leasta portion thereof. A plurality of attachment tabs extend away from theelectrode-carrying surface, where the tabs are arranged to permitselective ones thereof to be wrapped around a blood vessel while othersof the tabs may be selectively removed. The electrode structure on orover the electrode-carrying surface.

In preferred embodiments, the base includes at least one tab whichextends longitudinally from the electrode-carrying surface and at leasttwo tabs which extend away from the surface at opposite, transverseangles. In an even more preferred embodiment, the electrode-carryingsurface is rectangular, and at least two longitudinally extending tabsextend from adjacent corners of the rectangular surface. The twotransversely angled tabs extend at a transverse angle away from the sametwo corners.

As with prior embodiments, the electrode structure preferably includesone or more stretchable electrodes secured to the electrode-carryingsurface. The stretchable electrodes are preferably elongated coils, morepreferably being “flattened coils” to enhance electrical contact withthe blood vessel to be treated. The base is preferably an elastic base,more preferably being formed from an elastomeric sheet. The phrase“flattened coil,” as used herein, refers to an elongate electrodestructure including a plurality of successive turns where thecross-sectional profile is non-circular and which includes at least onegenerally flat or minimally curved face. Such coils may be formed byphysically deforming (flattening) a circular coil, e.g., as shown inFIG. 24 described below. Usually, the flattened coils will have across-section that has a width in the plane of the electrode assemblygreater than its height normal to the electrode assembly plane.Alternatively, the coils may be initially fabricated in the desiredgeometry having one generally flat (or minimally curved) face forcontacting tissue. Fully flattened coils, e.g., those having planarserpentine configurations, may also find use, but usually it will bepreferred to retain at least some thickness in the direction normal tothe flat or minimally curved tissue-contacting surface. Such thicknesshelps the coiled electrode protrude from the base and provide improvedtissue contact over the entire flattened surface.

In a still further aspect of the present invention, a method forwrapping an electrode assembly over a blood vessel comprises providingan electrode assembly having an elastic base and one or more stretchableelectrodes. The base is conformed over an exterior of the blood vessel,such as a carotid artery, and at least a portion of an electrode isstretched along with the base. Ends of the elastic base are securedtogether to hold the electrode assembly in place, typically with boththe elastic backing and stretchable electrode remaining under at leastslight tension to promote conformance to the vessel exterior. Theelectrode assembly will be located over a target site in the bloodvessel, typically a target site having an electrically activatedreceptor. Advantageously, the electrode structures of the presentinvention when wrapped under tension will flex and stretch withexpansions and contractions of the blood vessel. A presently preferredtarget site is a baroreceptor, particularly baroreceptors in or near thecarotid sinus.

In a still further aspect of the present invention, a method forwrapping an electrode assembly over a blood vessel comprises providingan electrode assembly including a base having an electrode-carryingsurface and an electrode structure on the electrode-carrying surface.The base is wrapped over a blood vessel, and some but not all of aplurality of attachment tags on the base are secured over the bloodvessel. Usually, the tabs which are not used to secure an electrodeassembly will be removed, typically by cutting. Preferred target sitesare electrically activated receptors, usually baroreceptors, moreusually baroreceptors on the carotid sinus. The use of such electrodeassemblies having multiple attachment tabs is particularly beneficialwhen securing the electrode assembly on a carotid artery near thecarotid sinus. By using particular tabs, as described in more detailbelow, the active electrode area can be positioned at any of a varietyof locations on the common, internal, and/or external carotid arteries.

In another aspect, the present invention comprises pressure measuringassemblies including an elastic base adapted to be mounted on the outerwall of a blood vessel under circumferential tension. A strainmeasurement sensor is positioned on the base to measure strain resultingfrom circumferential expansion of the vessel due to a blood pressureincrease. Usually, the base will wrap about the entire circumference ofthe vessel, although only a portion of the base need be elastic.Alternatively, a smaller base may be stapled, glued, clipped orotherwise secured over a “patch” of the vessel wall to detect strainvariations over the underlying surface. Exemplary sensors include straingauges and micro machined sensors (MEMS).

In yet another aspect, electrode assemblies according to the presentinvention comprise a base and at least three parallel elongate electrodestructures secured over a surface of the base. The base is attachable toan outside surface of a blood vessel, such as a carotid artery,particularly a carotid artery near the carotid sinus, and has a lengthsufficient to extend around at least a substantial portion of thecircumference of the blood vessel, typically extending around at least25% of the circumference, usually extending around at least 50% of thecircumference, preferably extending at least 66% of the circumference,and often extending around at least 75% of or the entire circumferenceof the blood vessel. As with prior embodiments, the base will preferablybe elastic and composed of any of the materials set forth previously.

The at least three parallel elongate electrode structures willpreferably be aligned in the circumferential direction of the base,i.e., the axis or direction of the base which will be alignedcircumferentially over the blood vessel when the base is mounted on theblood vessel. The electrode structures will preferably be stretchable,typically being elongate coils, often being flattened elongate coils, asalso described previously.

At least an outer pair of the electrode structures will be electricallyisolated from an inner electrode structure, and the outer electrodestructures will preferably be arranged in a U-pattern in order tosurround the inner electrode structure. In this way, the outer pair ofelectrodes can be connected using a single conductor taken from thebase, and the outer electrode structures and inner electrode structuremay be connected to separate poles on a power supply in order to operatein the “pseudo” tripolar mode described herein below.

To address low blood pressure and other conditions requiring bloodpressure augmentation, the present invention provides electrode designsand methods utilizing such electrodes by which the blood pressure may beselectively and controllably regulated by inhibiting or dampeningbaroreceptor signals. By selectively and controllably inhibiting ordampening baroreceptor signals, the present invention reduces conditionsassociated with low blood pressure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of the upper torso of a human bodyshowing the major arteries and veins and associated anatomy.

FIG. 2A is a cross-sectional schematic illustration of the carotid sinusand baroreceptors within the vascular wall.

FIG. 2B is a schematic illustration of baroreceptors within the vascularwall and the baroreflex system.

FIG. 3 is a schematic illustration of a baroreceptor activation systemin accordance with the present invention.

FIGS. 4A and 4B are schematic illustrations of a baroreceptor activationdevice in the form of an implantable extra luminal conductive structurewhich electrically induces a baroreceptor signal in accordance with anembodiment of the present invention.

FIGS. 5A-5F are schematic illustrations of various possible arrangementsof electrodes around the carotid sinus for extravascular electricalactivation embodiments.

FIG. 6 is a schematic illustration of a serpentine shaped electrode forextravascular electrical activation embodiments.

FIG. 7 is a schematic illustration of a plurality of electrodes alignedorthogonal to the direction of wrapping around the carotid sinus forextravascular electrical activation embodiments.

FIGS. 8-11 are schematic illustrations of various multi-channelelectrodes for extravascular electrical activation embodiments.

FIG. 12 is a schematic illustration of an extravascular electricalactivation device including a tether and an anchor disposed about thecarotid sinus and common carotid artery.

FIG. 13 is a schematic illustration of an alternative extravascularelectrical activation device including a plurality of ribs and a spine.

FIG. 14 is a schematic illustration of an electrode assembly forextravascular electrical activation embodiments.

FIG. 15 is a schematic illustration of a fragment of an alternativecable for use with an electrode assembly such as shown in FIG. 14.

FIG. 16 illustrates a foil strain gauge for measuring expansion force ofa carotid artery or other blood vessel.

FIG. 17 illustrates a transducer which is adhesively connected to thewall of an artery.

FIG. 18 is a cross-sectional view of the transducer of FIG. 17.

FIG. 19 illustrates a first exemplary electrode assembly having anelastic base and plurality of attachment tabs.

FIG. 20 is a more detailed illustration of the electrode-carryingsurface of the electrode assembly of FIG. 19.

FIG. 21 is a detailed illustration of electrode coils which are presentin an elongate lead of the electrode assembly of FIG. 19.

FIG. 22 is a detailed view of the electrode-carrying surface of anelectrode assembly similar to that shown in FIG. 20, except that theelectrodes have been flattened.

FIG. 23 is a cross-sectional view of the electrode structure of FIG. 22.

FIG. 24 illustrates the transition between the flattened andnon-flattened regions of the electrode coil of the electrode assemblyFIG. 20.

FIG. 25 is a cross-sectional view taken along the line 25-25 of FIG. 24.

FIG. 26 is a cross-sectional view taken along the line 26-26 of FIG. 24.

FIG. 27 is an illustration of a further exemplary electrode assemblyconstructed in accordance with the principles of the present invention.

FIG. 28 illustrates the electrode assembly of FIG. 27 wrapped around thecommon carotid artery near the carotid bifurcation.

FIG. 29 illustrates the electrode assembly of FIG. 27 wrapped around theinternal carotid artery.

FIG. 30 is similar to FIG. 29, but with the carotid bifurcation having adifferent geometry.

FIGS. 31A and 31B are schematic illustrations of a baroreceptoractivation device in the form of a fluid delivery device which may beused to deliver an agent which chemically or biologically induces abaroreceptor signal in accordance with an embodiment of the presentinvention.

FIGS. 32A and 32B are schematic illustrations of a baroreceptoractivation device in the form of an internal inflatable balloon whichmechanically induces a baroreceptor signal in accordance with anembodiment of the present invention.

FIGS. 33A and 33B are schematic illustrations of a baroreceptoractivation device in the form of an external pressure cuff whichmechanically induces a baroreceptor signal in accordance with anembodiment of the present invention.

FIGS. 34A and 34B are schematic illustrations of a baroreceptoractivation device in the form of an internal deformable coil structurewhich mechanically induces a baroreceptor signal in accordance with anembodiment of the present invention.

FIGS. 34C and 34D are cross-sectional views of alternative embodimentsof the coil member illustrated in FIGS. 34A and 34B.

FIGS. 35A and 35B are schematic illustrations of a baroreceptoractivation device in the form of an external deformable coil structurewhich mechanically induces a baroreceptor signal in accordance with anembodiment of the present invention.

FIGS. 35C and 35D are cross-sectional views of alternative embodimentsof the coil member illustrated in FIGS. 35A and 35B.

FIGS. 36A and 36B are schematic illustrations of a baroreceptoractivation device in the form of an external flow regulator whichartificially creates back pressure to induce a baroreceptor signal inaccordance with an embodiment of the present invention.

FIGS. 37A and 37B are schematic illustrations of a baroreceptoractivation device in the form of an internal flow regulator whichartificially creates back pressure to induce a baroreceptor signal inaccordance with an embodiment of the present invention.

FIGS. 38A and 38B are schematic illustrations of a baroreceptoractivation device in the form of a magnetic device which mechanicallyinduces a baroreceptor signal in accordance with an embodiment of thepresent invention.

FIGS. 39A and 39B are schematic illustrations of a baroreceptoractivation device in the form of a transducer which mechanically inducesa baroreceptor signal in accordance with an embodiment of the presentinvention.

FIGS. 40A and 40B are schematic illustrations of a baroreceptoractivation device in the form of an internal conductive structure whichelectrically or thermally induces a baroreceptor signal in accordancewith an embodiment of the present invention.

FIGS. 41A and 41B are schematic illustrations of a baroreceptoractivation device in the form of an internal conductive structure,activated by an internal inductor, which electrically or thermallyinduces a baroreceptor signal in accordance with an embodiment of thepresent invention.

FIGS. 42A and 42B are schematic illustrations of a baroreceptoractivation device in the form of an internal conductive structure,activated by an internal inductor located in an adjacent vessel, whichelectrically or thermally induces a baroreceptor signal in accordancewith an embodiment of the present invention.

FIGS. 43A and 43B are schematic illustrations of a baroreceptoractivation device in the form of an internal conductive structure,activated by an external inductor, which electrically or thermallyinduces a baroreceptor signal in accordance with an embodiment of thepresent invention.

FIGS. 44A and 44B are schematic illustrations of a baroreceptoractivation device in the form of an internal bipolar conductivestructure which electrically or thermally induces a baroreceptor signalin accordance with an embodiment of the present invention;

FIGS. 45A and 45B are schematic illustrations of a baroreceptoractivation device in the form of an electromagnetic field responsivedevice which electrically or thermally induces a baroreceptor signal inaccordance with an embodiment of the present invention;

FIGS. 46A and 46B are schematic illustrations of a baroreceptoractivation device in the form of an external Peltier device whichthermally induces a baroreceptor signal in accordance with an embodimentof the present invention; and

FIGS. 47A-47C are schematic illustrations of a preferred embodiment ofan inductively activated electrically conductive structure.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description should be read with reference to thedrawings in which similar elements in different drawings are numberedthe same. The drawings, which are not necessarily to scale, depictillustrative embodiments and are not intended to limit the scope of theinvention.

To better understand the present invention, it may be useful to explainsome of the basic vascular anatomy associated with the cardiovascularsystem. Refer to FIG. 1 which is a schematic illustration of the uppertorso of a human body 10 showing some of the major arteries and veins ofthe cardiovascular system. The left ventricle of the heart 11 pumpsoxygenated blood up into the aortic arch 12. The right subclavian artery13, the right common carotid artery 14, the left common carotid artery15 and the left subclavian artery 16 branch off the aortic arch 12proximal of the descending thoracic aorta 17. Although relatively short,a distinct vascular segment referred to as the brachiocephalic artery 22connects the right subclavian artery 13 and the right common carotidartery 14 to the aortic arch 12. The right carotid artery 14 bifurcatesinto the right external carotid artery 18 and the right internal carotidartery 19 at the right carotid sinus 20. Although not shown for purposesof clarity only, the left carotid artery 15 similarly bifurcates intothe left external carotid artery and the left internal carotid artery atthe left carotid sinus.

From the aortic arch 12, oxygenated blood flows into the carotidarteries 18/19 and the subclavian arteries 13/16. From the carotidarteries 18/19, oxygenated blood circulates through the head andcerebral vasculature and oxygen depleted blood returns to the heart 11by way of the jugular veins, of which only the right internal jugularvein 21 is shown for sake of clarity. From the subclavian arteries13/16, oxygenated blood circulates through the upper peripheralvasculature and oxygen depleted blood returns to the heart by way of thesubclavian veins, of which only the right subclavian vein 23 is shown,also for sake of clarity. The heart 11 pumps the oxygen depleted bloodthrough the pulmonary system where it is re-oxygenated. There-oxygenated blood returns to the heart 11 which pumps there-oxygenated blood into the aortic arch as described above, and thecycle repeats.

Within the arterial walls of the aortic arch 12, common carotid arteries14/15 (near the right carotid sinus 20 and left carotid sinus),subclavian arteries 13/16 and brachiocephalic artery 22 there arebaroreceptors 30. For example, as best seen in FIG. 2A, baroreceptors 30reside within the vascular walls of the carotid sinus 20. Baroreceptors30 are a type of stretch receptor used by the body to sense bloodpressure. An increase in blood pressure causes the arterial wall tostretch, and a decrease in blood pressure causes the arterial wall toreturn to its original size. Such a cycle is repeated with each beat ofthe heart. Because baroreceptors 30 are located within the arterialwall, they are able to sense deformation of the adjacent tissue, whichis indicative of a change in blood pressure. The baroreceptors 30located in the right carotid sinus 20, the left carotid sinus and theaortic arch 12 play the most significant role in sensing blood pressurethat affects the baroreflex system 50, which is described in more detailwith reference to FIG. 2B.

Refer now to FIG. 2B, which shows a schematic illustration ofbaroreceptors 30 disposed in a generic vascular wall 40 and a schematicflow chart of the baroreflex system 50. Baroreceptors 30 are profuselydistributed within the arterial walls 40 of the major arteries discussedpreviously, and generally form an arbor 32. The baroreceptor arbor 32comprises a plurality of baroreceptors 30, each of which transmitsbaroreceptor signals to the brain 52 via nerve 38. The baroreceptors 30are so profusely distributed and arborized within the vascular wall 40that discrete baroreceptor arbors 32 are not readily discernable. Tothis end, those skilled in the art will appreciate that thebaroreceptors 30 shown in FIG. 2B are primarily schematic for purposesof illustration and discussion.

Baroreceptor signals are used to activate a number of body systems whichcollectively may be referred to as the baroreflex system 50.Baroreceptors 30 are connected to the brain 52 via the nervous system51. Thus, the brain 52 is able to detect changes in blood pressure,which is indicative of cardiac output. If cardiac output is insufficientto meet demand (i.e., the heart 11 is unable to pump sufficient blood),the baroreflex system 50 activates a number of body systems, includingthe heart 11, kidneys 53, vessels 54, and other organs/tissues. Suchactivation of the baroreflex system 50 generally corresponds to anincrease in neurohormonal activity. Specifically, the baroreflex system50 initiates a neurohormonal sequence that signals the heart 11 toincrease heart rate and increase contraction force in order to increasecardiac output, signals the kidneys 53 to increase blood volume byretaining sodium and water, and signals the vessels 54 to constrict toelevate blood pressure. The cardiac, renal and vascular responsesincrease blood pressure and cardiac output 55, and thus increase theworkload of the heart 11. In a patient with heart failure, this furtheraccelerates myocardial damage and exacerbates the heart failure state.

To address the problems of hypertension, heart failure, othercardiovascular disorders and renal disorders, the present inventionbasically provides a number of devices, systems and methods by which thebaroreflex system 50 is activated to reduce excessive blood pressure,autonomic nervous system activity and neurohormonal activation. Inparticular, the present invention provides a number of devices, systemsand methods by which baroreceptors 30 may be activated, therebyindicating an increase in blood pressure and signaling the brain 52 toreduce the body's blood pressure and level of sympathetic nervous systemand neurohormonal activation, and increase parasypathetic nervous systemactivation, thus having a beneficial effect on the cardiovascular systemand other body systems.

With reference to FIG. 3, the present invention generally provides asystem including a control system 60, a baroreceptor activation device70, and a sensor 80 (optional), which generally operate in the followingmanner. The sensor(s) 80 optionally senses and/or monitors a parameter(e.g., cardiovascular function) indicative of the need to modify thebaroreflex system and generates a signal indicative of the parameter.The control system 60 generates a control signal as a function of thereceived sensor signal. The control signal activates, deactivates orotherwise modulates the baroreceptor activation device 70. Typically,activation of the device 70 results in activation of the baroreceptors30. Alternatively, deactivation or modulation of the baroreceptoractivation device 70 may cause or modify activation of the baroreceptors30. The baroreceptor activation device 70 may comprise a wide variety ofdevices which utilize electrical means to activate baroreceptors 30.Thus, when the sensor 80 detects a parameter indicative of the need tomodify the baroreflex system activity (e.g., excessive blood pressure),the control system 60 generates a control signal to modulate (e.g.activate) the baroreceptor activation device 70 thereby inducing abaroreceptor 30 signal that is perceived by the brain 52 to be apparentexcessive blood pressure. When the sensor 80 detects a parameterindicative of normal body function (e.g., normal blood pressure), thecontrol system 60 generates a control signal to modulate (e.g.,deactivate) the baroreceptor activation device 70.

As mentioned previously, the baroreceptor activation device 70 maycomprise a wide variety of devices which utilize mechanical, electrical,thermal, chemical, biological or other means to activate thebaroreceptors 30. Specific embodiments of the generic baroreceptoractivation device 70 are discussed with reference to FIGS. 4A-4B and31A-47C. In most instances, particularly the mechanical activationembodiments, the baroreceptor activation device 70 indirectly activatesone or more baroreceptors 30 by stretching or otherwise deforming thevascular wall 40 surrounding the baroreceptors 30. In some otherinstances, particularly the non-mechanical activation embodiments, thebaroreceptor activation device 70 may directly activate one or morebaroreceptors 30 by changing the electrical, thermal or chemicalenvironment or potential across the baroreceptors 30. It is alsopossible that changing the electrical potential across the tissuesurrounding the baroreceptors 30 may cause the surrounding tissue tostretch or otherwise deform, thus mechanically activating thebaroreceptors 30, in which case the stretchable and elastic electrodestructures of the present invention may provide significant advantages.It is also possible that changing the thermal or chemical potentialacross the tissue surrounding the baroreceptors 30 may cause thesurrounding tissue to stretch or otherwise deform, thus mechanicallyactivating the baroreceptors 30. In other instances, particularly thebiological activation embodiments, a change in the function orsensitivity of the baroreceptors 30 may be induced by changing thebiological activity in the baroreceptors 30 and altering theirintracellular makeup and function.

All of the specific embodiments of the electrode structures of thepresent invention are suitable for implantation, and are preferablyimplanted using a minimally invasive surgical approach. The baroreceptoractivation device 70 may be positioned anywhere baroreceptors 30 arepresent. Such potential implantation sites are numerous, such as theaortic arch 12, in the common carotid arteries 18/19 near the carotidsinus 20, in the subclavian arteries 13/16, in the brachiocephalicartery 22, or in other arterial or venous locations. The electrodestructures of the present invention will be implanted such that they arepositioned on or over a vascular structure immediately adjacent thebaroreceptors 30. Preferably, the electrode structure of thebaroreceptor activation device 70 is implanted near the right carotidsinus 20 and/or the left carotid sinus (near the bifurcation of thecommon carotid artery) and/or the aortic arch 12, where baroreceptors 30have a significant impact on the baroreflex system 50. For purposes ofillustration only, the present invention is described with reference tobaroreceptor activation device 70 positioned near the carotid sinus 20.

The optional sensor 80 is operably coupled to the control system 60 byelectric sensor cable or lead 82. The sensor 80 may comprise anysuitable device that measures or monitors a parameter indicative of theneed to modify the activity of the baroreflex system. For example, thesensor 80 may comprise a physiologic transducer or gauge that measuresECG, blood pressure (systolic, diastolic, average or pulse pressure),blood volumetric flow rate, blood flow velocity, blood pH, O 2 or CO 2content, mixed venous oxygen saturation (SVO 2), vasoactivity, nerveactivity, tissue activity, body movement, activity levels, respiration,or composition. Examples of suitable transducers or gauges for thesensor 80 include ECG electrodes, a piezoelectric pressure transducer,an ultrasonic flow velocity transducer, an ultrasonic volumetric flowrate transducer, a thermodilution flow velocity transducer, a capacitivepressure transducer, a membrane pH electrode, an optical detector (SVO2), tissue impedance (electrical), or a strain gauge. Although only onesensor 80 is shown, multiple sensors 80 of the same or different type atthe same or different locations may be utilized.

An example of an implantable blood pressure measurement device that maybe disposed about a blood vessel is disclosed in U.S. Pat. No. 6,106,477to Miesel et al., the entire disclosure of which is incorporated hereinby reference. An example of a subcutaneous ECG monitor is available fromMedtronic under the trade name REVEAL ILR and is disclosed in PCTPublication No. WO 98/02209, the entire disclosure of which isincorporated herein by reference. Other examples are disclosed in U.S.Pat. Nos. 5,987,352 and 5,331,966, the entire disclosures of which areincorporated herein by reference. Examples of devices and methods formeasuring absolute blood pressure utilizing an ambient pressurereference are disclosed in U.S. Pat. No. 5,810,735 to Halperin et al.,U.S. Pat. No. 5,904,708 to Goedeke, and PCT Publication No. WO 00/16686to Brockway et al., the entire disclosures of which are incorporatedherein by reference. The sensor 80 described herein may take the form ofany of these devices or other devices that generally serve the samepurpose.

The sensor 80 is preferably positioned in a chamber of the heart 11, orin/on a major artery such as the aortic arch 12, a common carotid artery14/15, a subclavian artery 13/16 or the brachiocephalic artery 22, suchthat the parameter of interest may be readily ascertained. The sensor 80may be disposed inside the body such as in or on an artery, a vein or anerve (e.g. vagus nerve), or disposed outside the body, depending on thetype of transducer or gauge utilized. The sensor 80 may be separate fromthe baroreceptor activation device 70 or combined therewith. Forpurposes of illustration only, the sensor 80 is shown positioned on theright subclavian artery 13.

By way of example, the control system 60 includes a control block 61comprising a processor 63 and a memory 62. Control system 60 isconnected to the sensor 80 by way of sensor cable 82. Control system 60is also connected to the baroreceptor activation device 70 by way ofelectric control cable 72. Thus, the control system 60 receives a sensorsignal from the sensor 80 by way of sensor cable 82, and transmits acontrol signal to the baroreceptor activation device 70 by way ofcontrol cable 72.

The system components 60/70/80 may be directly linked via cables 72/82or by indirect means such as RF signal transceivers, ultrasonictransceivers or galvanic couplings. Examples of such indirectinterconnection devices are disclosed in U.S. Pat. No. 4,987,897 toFunke and U.S. Pat. No. 5,113,859 to Funke, the entire disclosures ofwhich are incorporated herein by reference.

The memory 62 may contain data related to the sensor signal, the controlsignal, and/or values and commands provided by the input device 64. Thememory 62 may also include software containing one or more algorithmsdefining one or more functions or relationships between the controlsignal and the sensor signal. The algorithm may dictate activation ordeactivation control signals depending on the sensor signal or amathematical derivative thereof. The algorithm may dictate an activationor deactivation control signal when the sensor signal falls below alower predetermined threshold value, rises above an upper predeterminedthreshold value or when the sensor signal indicates a specificphysiologic event. The algorithm may dynamically alter the thresholdvalue as determined by the sensor input values.

As mentioned previously, the baroreceptor activation device 70 activatesbaroreceptors 30 electrically, optionally in combination withmechanical, thermal, chemical, biological or other co-activation. Insome instances, the control system 60 includes a driver 66 to providethe desired power mode for the baroreceptor activation device 70. Forexample, the driver 66 may comprise a power amplifier or the like andthe cable 72 may comprise electrical lead(s). In other instances, thedriver 66 may not be necessary, particularly if the processor 63generates a sufficiently strong electrical signal for low levelelectrical actuation of the baroreceptor activation device 70.

The control system 60 may operate as a closed loop utilizing feedbackfrom the sensor 80, or other sensors, such as heart rate sensors whichmay be incorporated or the electrode assembly, or as an open looputilizing reprogramming commands received by input device 64. The closedloop operation of the control system 60 preferably utilizes somefeedback from the transducer 80, but may also operate in an open loopmode without feedback. Programming commands received by the input device64 may directly influence the control signal, the output activationparameters, or may alter the software and related algorithms containedin memory 62. The treating physician and/or patient may provide commandsto input device 64. Display 65 may be used to view the sensor signal,control signal and/or the software/data contained in memory 62.

The control signal generated by the control system 60 may be continuous,periodic, alternating, episodic or a combination thereof, as dictated byan algorithm contained in memory 62. Continuous control signals includea constant pulse, a constant train of pulses, a triggered pulse and atriggered train of pulses. Examples of periodic control signals includeeach of the continuous control signals described above which have adesignated start time (e.g., beginning of each period as designated byminutes, hours, or days in combinations of) and a designated duration(e.g., seconds, minutes, hours, or days in combinations of). Examples ofalternating control signals include each of the continuous controlsignals as described above which alternate between the right and leftoutput channels. Examples of episodic control signals include each ofthe continuous control signals described above which are triggered by anepisode (e.g., activation by the physician/patient, an increase/decreasein blood pressure above a certain threshold, heart rate above/belowcertain levels, etc.).

The stimulus regimen governed by the control system 60 may be selectedto promote long term efficacy. It is theorized that uninterrupted orotherwise unchanging activation of the baroreceptors 30 may result inthe baroreceptors and/or the baroreflex system becoming less responsiveover time, thereby diminishing the long term effectiveness of thetherapy. Therefore, the stimulus regimen maybe selected to activate,deactivate or otherwise modulate the baroreceptor activation device 70in such a way that therapeutic efficacy is maintained preferably foryears.

In addition to maintaining therapeutic efficacy over time, the stimulusregimens of the present invention may be selected reduce powerrequirement/consumption of the system 60. As will be described in moredetail hereinafter, the stimulus regimen may dictate that thebaroreceptor activation device 70 be initially activated at a relativelyhigher energy and/or power level, and subsequently activated at arelatively lower energy and/or power level. The first level attains thedesired initial therapeutic effect, and the second (lower) levelsustains the desired therapeutic effect long term. By reducing theenergy and/or power levels after the desired therapeutic effect isinitially attained, the energy required or consumed by the activationdevice 70 is also reduced long term. This may correlate into systemshaving greater longevity and/or reduced size (due to reductions in thesize of the power supply and associated components).

A first general approach for a stimulus regimen which promotes long termefficacy and reduces power requirements/consumption involves generatinga control signal to cause the baroreceptor activation device 70 to havea first output level of relatively higher energy and/or power, andsubsequently changing the control signal to cause the baroreceptoractivation device 70 to have a second output level of relatively lowerenergy and/or power. The first output level may be selected andmaintained for sufficient time to attain the desired initial effect(e.g., reduced heart rate and/or blood pressure), after which the outputlevel may be reduced to the second level for sufficient time to sustainthe desired effect for the desired period of time.

For example, if the first output level has a power and/or energy valueof X1, the second output level may have a power and/or energy value ofX2, wherein X2 is less than X1. In some instances, X2 may be equal tozero, such that the first level is “on” and the second level is “off”.It is recognized that power and energy refer to two differentparameters, and in some cases, a change in one of the parameters (poweror energy) may not correlate to the same or similar change in the otherparameter. In the present invention, it is contemplated that a change inone or both of the parameters may be suitable to obtain the desiredresult of promoting long term efficacy.

It is also contemplated that more than two levels may be used. Eachfurther level may increase the output energy or power to attain thedesired effect, or decrease the output energy or power to retain thedesired effect. For example, in some instances, it may be desirable tohave further reductions in the output level if the desired effect may besustained at lower power or energy levels. In other instances,particularly when the desired effect is diminishing or is otherwise notsustained, it may be desirable to increase the output level until thedesired effect is reestablished, and subsequently decrease the outputlevel to sustain the effect.

The transition from each level may be a step function (e.g., a singlestep or a series of steps), a gradual transition over a period of time,or a combination thereof. In addition, the signal levels may becontinuous, periodic, alternating, or episodic as discussed previously.

In electrical activation using a non modulated signal, the output (poweror energy) level of the baroreceptor activation device 70 may be changedby adjusting the output signal voltage level, current level and/orsignal duration. The output signal of the baroreceptor activation device70 may be, for example, constant current or constant voltage. Inelectrical activation embodiments using a modulated signal, wherein theoutput signal comprises, for example, a series of pulses, several pulsecharacteristics may be changed individually or in combination to changethe power or energy level of the output signal. Such pulsecharacteristics include, but are not limited to: pulse amplitude (PA),pulse frequency (PF), pulse width or duration (PW), pulse waveform(square, triangular, sinusoidal, etc.), pulse polarity (for bipolarelectrodes) and pulse phase (monophasic, biphasic).

In electrical activation wherein the output signal comprises a pulsetrain, several other signal characteristics may be changed in additionto the pulse characteristics described above, as described in commonlyassigned U.S. Pat. No. 6,985,774, the full disclosure of which isincorporated herein by reference.

The control system 60 may be implanted in whole or in part. For example,the entire control system 60 may be carried externally by the patientutilizing transdermal connections to the sensor lead 82 and the controllead 72. Alternatively, the control block 61 and driver 66 may beimplanted with the input device 64 and display 65 carried externally bythe patient utilizing transdermal connections therebetween. As a furtheralternative, the transdermal connections may be replaced by cooperatingtransmitters/receivers to remotely communicate between components of thecontrol system 60 and/or the sensor 80 and baroreceptor activationdevice 70.

With general reference to FIGS. 4A-4B and 31A-47C, schematicillustrations of specific embodiments of the baroreceptor activationdevice 70 are shown. The design, function and use of these specificembodiments, in addition to the control system 60 and sensor 80 (notshown), are the same as described with reference to FIG. 3, unlessotherwise noted or apparent from the description. In addition, theanatomical features illustrated in FIGS. 4A-4B and 31A-47C are the sameas discussed with reference to FIGS. 1, 2A and 2B, unless otherwisenoted. In each embodiment, the connections between the components60/70/80 may be physical (e.g., wires, tubes, cables, etc.) or remote(e.g., transmitter/receiver, inductive, magnetic, etc.). For physicalconnections, the connection may travel intraarterially, intravenously,subcutaneously, or through other natural tissue paths.

Refer now to FIGS. 5A-5F which show schematic illustrations of variouspossible arrangements of electrodes around the carotid sinus 20 forextravascular electrical activation embodiments, such as baroreceptoractivation device 300 described with reference to FIGS. 4A and 4B. Theelectrode designs illustrated and described hereinafter may beparticularly suitable for connection to the carotid arteries at or nearthe carotid sinus, and may be designed to minimize extraneous tissuestimulation.

In FIGS. 5A-5F, the carotid arteries are shown, including the common 14,the external 18 and the internal 19 carotid arteries. The location ofthe carotid sinus 20 may be identified by a landmark bulge 21, which istypically located on the internal carotid artery 19 just distal of thebifurcation, or extends across the bifurcation from the common carotidartery 14 to the internal carotid artery 19.

The carotid sinus 20, and in particular the bulge 21 of the carotidsinus, may contain a relatively high density of baroreceptors 30 (notshown) in the vascular wall. For this reason, it may be desirable toposition the electrodes 302 of the activation device 300 on and/oraround the sinus bulge 21 to maximize baroreceptor responsiveness and tominimize extraneous tissue stimulation.

It should be understood that the device 300 and electrodes 302 aremerely schematic, and only a portion of which may be shown, for purposesof illustrating various positions of the electrodes 302 on and/or aroundthe carotid sinus 20 and the sinus bulge 21. In each of the embodimentsdescribed herein, the electrodes 302 may be monopolar, bipolar, ortripolar (anode-cathode-anode or cathode-anode-cathode sets). Specificextravascular electrode designs are described in more detailhereinafter.

In FIG. 5A, the electrodes 302 of the extravascular electricalactivation device 300 extend around a portion or the entirecircumference of the sinus 20 in a circular fashion. Often, it would bedesirable to reverse the illustrated electrode configuration in actualuse. In FIG. 5B, the electrodes 302 of the extravascular electricalactivation device 300 extend around a portion or the entirecircumference of the sinus 20 in a helical fashion. In the helicalarrangement shown in FIG. 5B, the electrodes 302 may wrap around thesinus 20 any number of times to establish the desired electrode 302contact and coverage. In the circular arrangement shown in FIG. 5A, asingle pair of electrodes 302 may wrap around the sinus 20, or aplurality of electrode pairs 302 may be wrapped around the sinus 20 asshown in FIG. 5C to establish more electrode 302 contact and coverage.

The plurality of electrode pairs 302 may extend from a point proximal ofthe sinus 20 or bulge 21, to a point distal of the sinus 20 or bulge 21to ensure activation of baroreceptors 30 throughout the sinus 20 region.The electrodes 302 may be connected to a single channel or multiplechannels as discussed in more detail hereinafter. The plurality ofelectrode pairs 302 may be selectively activated for purposes oftargeting a specific area of the sinus 20 to increase baroreceptorresponsiveness, or for purposes of reducing the exposure of tissue areasto activation to maintain baroreceptor responsiveness long term.

In FIG. 5D, the electrodes 302 extend around the entire circumference ofthe sinus 20 in a criss cross fashion. The criss cross arrangement ofthe electrodes 302 establishes contact with both the internal 19 andexternal 18 carotid arteries around the carotid sinus 20. Similarly, inFIG. 5E, the electrodes 302 extend around all or a portion of thecircumference of the sinus 20, including the internal 19 and external 18carotid arteries at the bifurcation, and in some instances the commoncarotid artery 14. In FIG. 5F, the electrodes 302 extend around all or aportion of the circumference of the sinus 20, including the internal 19and external 18 carotid arteries distal of the bifurcation. In FIGS. 5Eand 5F, the extravascular electrical activation devices 300 are shown toinclude a substrate or base structure 306 which may encapsulate andinsulate the electrodes 302 and may provide a means for attachment tothe sinus 20 as described in more detail hereinafter.

From the foregoing discussion with reference to FIGS. 5A-5F, it shouldbe apparent that there are a number of suitable arrangements for theelectrodes 302 of the activation device 300, relative to the carotidsinus 20 and associated anatomy. In each of the examples given above,the electrodes 302 are wrapped around a portion of the carotidstructure, which may require deformation of the electrodes 302 fromtheir relaxed geometry (e.g., straight). To reduce or eliminate suchdeformation, the electrodes 302 and/or the base structure 306 may have arelaxed geometry that substantially conforms to the shape of the carotidanatomy at the point of attachment. In other words, the electrodes 302and the base structure or backing 306 may be pre shaped to conform tothe carotid anatomy in a substantially relaxed state. Alternatively, theelectrodes 302 may have a geometry and/or orientation that reduces theamount of electrode 302 strain. Optionally, as described in more detailbelow, the backing or base structure 306 may be elastic or stretchableto facilitate wrapping of and conforming to the carotid sinus or othervascular structure.

For example, in FIG. 6, the electrodes 302 are shown to have aserpentine or wavy shape. The serpentine shape of the electrodes 302reduces the amount of strain seen by the electrode material when wrappedaround a carotid structure. In addition, the serpentine shape of theelectrodes increases the contact surface area of the electrode 302 withthe carotid tissue. As an alternative, the electrodes 302 may bearranged to be substantially orthogonal to the wrap direction (i.e.,substantially parallel to the axis of the carotid arteries) as shown inFIG. 7. In this alternative, the electrodes 302 each have a length and awidth or diameter, wherein the length is substantially greater than thewidth or diameter. The electrodes 302 each have a longitudinal axisparallel to the length thereof, wherein the longitudinal axis isorthogonal to the wrap direction and substantially parallel to thelongitudinal axis of the carotid artery about which the device 300 iswrapped. As with the multiple electrode embodiments describedpreviously, the electrodes 302 may be connected to a single channel ormultiple channels as discussed in more detail hereinafter.

Refer now to FIGS. 8-11 which schematically illustrate variousmulti-channel electrodes for the extravascular electrical activationdevice 300. FIG. 8 illustrates a six (6) channel electrode assemblyincluding six (6) separate elongate electrodes 302 extending adjacent toand parallel with each other. The electrodes 302 are each connected tomulti-channel cable 304. Some of the electrodes 302 may be common,thereby reducing the number of conductors necessary in the cable 304.

Base structure or substrate 306 may comprise a flexible and electricallyinsulating material suitable for implantation, such as silicone, perhapsreinforced with a flexible material such as polyester fabric. The base306 may have a length suitable to wrap around all (360°) or a portion(i.e., less than 360°) of the circumference of one or more of thecarotid arteries adjacent the carotid sinus 20. The electrodes 302 mayextend around a portion (i.e., less than 360° such as 270°, 180° or 90°)of the circumference of one or more of the carotid arteries adjacent thecarotid sinus 20. To this end, the electrodes 302 may have a length thatis less than (e.g., 75%, 50% or 25%) the length of the base 206. Theelectrodes 302 may be parallel, orthogonal or oblique to the length ofthe base 306, which is generally orthogonal to the axis of the carotidartery to which it is disposed about. Preferably, the base structure orbacking will be elastic (i.e., stretchable), typically being composed ofat least in part of silicone, latex, or other elastomer. If such elasticstructures are reinforced, the reinforcement should be arranged so thatit does not interfere with the ability of the base to stretch andconform to the vascular surface.

The electrodes 302 may comprise round wire, rectangular ribbon or foilformed of an electrically conductive and radiopaque material such asplatinum. The base structure 306 substantially encapsulates theelectrodes 302, leaving only an exposed area for electrical connectionto extravascular carotid sinus tissue. For example, each electrode 302may be partially recessed in the base 206 and may have one side exposedalong all or a portion of its length for electrical connection tocarotid tissue. Electrical paths through the carotid tissues may bedefined by one or more pairs of the elongate electrodes 302.

In all embodiments described with reference to FIGS. 8-11, themulti-channel electrodes 302 may be selectively activated for purposesof mapping and targeting a specific area of the carotid sinus 20 todetermine the best combination of electrodes 302 (e.g., individual pair,or groups of pairs) to activate for maximum baroreceptor responsiveness,as described elsewhere herein. In addition, the multi-channel electrodes302 may be selectively activated for purposes of reducing the exposureof tissue areas to activation to maintain long term efficacy asdescribed, as described elsewhere herein. For these purposes, it may beuseful to utilize more than two (2) electrode channels. Alternatively,the electrodes 302 may be connected to a single channel wherebybaroreceptors are uniformly activated throughout the sinus 20 region.

An alternative multi-channel electrode design is illustrated in FIG. 9.In this embodiment, the device 300 includes sixteen (16) individualelectrode pads 302 connected to 16 channel cable 304 via 4 channelconnectors 303. In this embodiment, the circular electrode pads 302 arepartially encapsulated by the base structure 306 to leave one face ofeach button electrode 302 exposed for electrical connection to carotidtissues. With this arrangement, electrical paths through the carotidtissues may be defined by one or more pairs (bipolar) or groups(tripolar) of electrode pads 302.

A variation of the multi-channel pad type electrode design isillustrated in FIG. 10. In this embodiment, the device 300 includessixteen (16) individual circular pad electrodes 302 surrounded bysixteen (16) rings 305, which collectively may be referred to asconcentric electrode pads 302/305. Pad electrodes 302 are connected to17 channel cable 304 via 4 channel connectors 303, and rings 305 arecommonly connected to 17 channel cable 304 via a single channelconnector 307. In this embodiment, the circular shaped electrodes 302and the rings 305 are partially encapsulated by the base structure 306to leave one face of each pad electrode 302 and one side of each ring305 exposed for electrical connection to carotid tissues. As analternative, two rings 305 may surround each electrode 302, with therings 305 being commonly connected. With these arrangements, electricalpaths through the carotid tissues may be defined between one or more padelectrode 302/ring 305 sets to create localized electrical paths.

Another variation of the multi-channel pad electrode design isillustrated in FIG. 11. In this embodiment, the device 300 includes acontrol IC chip 310 connected to 3 channel cable 304. The control chip310 is also connected to sixteen (16) individual pad electrodes 302 via4 channel connectors 303. The control chip 310 permits the number ofchannels in cable 304 to be reduced by utilizing a coding system. Thecontrol system 60 sends a coded control signal which is received by chip310. The chip 310 converts the code and enables or disables selectedelectrode 302 pairs in accordance with the code.

For example, the control signal may comprise a pulse wave form, whereineach pulse includes a different code. The code for each pulse causes thechip 310 to enable one or more pairs of electrodes, and to disable theremaining electrodes. Thus, the pulse is only transmitted to the enabledelectrode pair(s) corresponding to the code sent with that pulse. Eachsubsequent pulse would have a different code than the preceding pulse,such that the chip 310 enables and disables a different set ofelectrodes 302 corresponding to the different code. Thus, virtually anynumber of electrode pairs may be selectively activated using controlchip 310, without the need for a separate channel in cable 304 for eachelectrode 302. By reducing the number of channels in cable 304, the sizeand cost thereof may be reduced.

Optionally, the IC chip 310 may be connected to feedback sensor 80,taking advantage of the same functions as described with reference toFIG. 3. In addition, one or more of the electrodes 302 may be used asfeedback sensors when not enabled for activation. For example, such afeedback sensor electrode may be used to measure or monitor electricalconduction in the vascular wall to provide data analogous to an ECG.Alternatively, such a feedback sensor electrode may be used to sense achange in impedance due to changes in blood volume during a pulsepressure to provide data indicative of heart rate, blood pressure, orother physiologic parameter.

Refer now to FIG. 12 which schematically illustrates an extravascularelectrical activation device 300 including a support collar or anchor312. In this embodiment, the activation device 300 is wrapped around theinternal carotid artery 19 at the carotid sinus 20, and the supportcollar 312 is wrapped around the common carotid artery 14. Theactivation device 300 is connected to the support collar 312 by cables304, which act as a loose tether. With this arrangement, the collar 312isolates the activation device from movements and forces transmitted bythe cables 304 proximal of the support collar, such as may beencountered by movement of the control system 60 and/or driver 66. As analternative to support collar 312, a strain relief (not shown) may beconnected to the base structure 306 of the activation device 300 at thejuncture between the cables 304 and the base 306. With either approach,the position of the device 300 relative to the carotid anatomy may bebetter maintained despite movements of other parts of the system.

In this embodiment, the base structure 306 of the activation device 300may comprise molded tube, a tubular extrusion, or a sheet of materialwrapped into a tube shape utilizing a suture flap 308 with sutures 309as shown. The base structure 306 may be formed of a flexible andbiocompatible material such as silicone, which may be reinforced with aflexible material such as polyester fabric available under the tradename DACRON® to form a composite structure. The inside diameter of thebase structure 306 may correspond to the outside diameter of the carotidartery at the location of implantation, for example 6 to 8 mm. The wallthickness of the base structure 306 may be very thin to maintainflexibility and a low profile, for example less than 1 mm. If the device300 is to be disposed about a sinus bulge 21, a correspondingly shapedbulge may be formed into the base structure for added support andassistance in positioning.

The electrodes 302 (shown in phantom) may comprise round wire,rectangular ribbon or foil, formed of an electrically conductive andradiopaque material such as platinum or platinum iridium. The electrodesmay be molded into the base structure 306 or adhesively connected to theinside diameter thereof, leaving a portion of the electrode exposed forelectrical connection to carotid tissues. The electrodes 302 mayencompass less than the entire inside circumference (e.g., 300°) of thebase structure 306 to avoid shorting. The electrodes 302 may have any ofthe shapes and arrangements described previously. For example, as shownin FIG. 12, two rectangular ribbon electrodes 302 may be used, eachhaving a width of 1 mm spaced 1.5 mm apart.

The support collar 312 may be formed similarly to base structure 306.For example, the support collar may comprise molded tube, a tubularextrusion, or a sheet of material wrapped into a tube shape utilizing asuture flap 315 with sutures 313 as shown. The support collar 312 may beformed of a flexible and biocompatible material such as silicone, whichmay be reinforced to form a composite structure. The cables 304 aresecured to the support collar 312, leaving slack in the cables 304between the support collar 312 and the activation device 300.

In all embodiments described herein, it may be desirable to secure theactivation device to the vascular wall using sutures or other fixationmeans. For example, sutures 311 may be used to maintain the position ofthe electrical activation device 300 relative to the carotid anatomy (orother vascular site containing baroreceptors). Such sutures 311 may beconnected to base structure 306, and pass through all or a portion ofthe vascular wall. For example, the sutures 311 may be threaded throughthe base structure 306, through the adventitia of the vascular wall, andtied. If the base structure 306 comprises a patch or otherwise partiallysurrounds the carotid anatomy, the corners and/or ends of the basestructure may be sutured, with additional sutures evenly distributedtherebetween. In order to minimize the propagation of a hole or a tearthrough the base structure 306, a reinforcement material such aspolyester fabric may be embedded in the silicone material. In additionto sutures, other fixation means may be employed such as staples or abiocompatible adhesive, for example.

Refer now to FIG. 13 which schematically illustrates an alternativeextravascular electrical activation device 300 including one or moreelectrode ribs 316 interconnected by spine 317. Optionally, a supportcollar 312 having one or more (non electrode) ribs 316 may be used toisolate the activation device 300 from movements and forces transmittedby the cables 304 proximal of the support collar 312.

The ribs 316 of the activation device 300 are sized to fit about thecarotid anatomy, such as the internal carotid artery 19 adjacent thecarotid sinus 20. Similarly, the ribs 316 of the support collar 312 maybe sized to fit about the carotid anatomy, such as the common carotidartery 14 proximal of the carotid sinus 20. The ribs 316 may beseparated, placed on a carotid artery, and closed thereabout to securethe device 300 to the carotid anatomy.

Each of the ribs 316 of the device 300 includes an electrode 302 on theinside surface thereof for electrical connection to carotid tissues. Theribs 316 provide insulating material around the electrodes 302, leavingonly an inside portion exposed to the vascular wall. The electrodes 302are coupled to the multi-channel cable 304 through spine 317. Spine 317also acts as a tether to ribs 316 of the support collar 312, which donot include electrodes since their function is to provide support. Themulti-channel electrode 302 functions discussed with reference to FIGS.8-11 are equally applicable to this embodiment.

The ends of the ribs 316 may be connected (e.g., sutured) after beingdisposed about a carotid artery, or may remain open as shown. If theends remain open, the ribs 316 may be formed of a relatively stiffmaterial to ensure a mechanical lock around the carotid artery. Forexample, the ribs 316 may be formed of polyethylene, polypropylene,PTFE, or other similar insulating and biocompatible material.Alternatively, the ribs 316 may be formed of a metal such as stainlesssteel or a nickel titanium alloy, as long as the metallic material waselectrically isolated from the electrodes 302. As a further alternative,the ribs 316 may comprise an insulating and biocompatible polymericmaterial with the structural integrity provided by metallic (e.g.,stainless steel, nickel titanium alloy, etc.) reinforcement. In thislatter alternative, the electrodes 302 may comprise the metallicreinforcement.

Refer now to FIG. 14 which schematically illustrates a specific exampleof an electrode assembly for an extravascular electrical activationdevice 300. In this specific example, the base structure 306 comprises asilicone sheet having a length of 5.0 inches, a thickness of 0.007inches, and a width of 0.312 inches. The electrodes 302 compriseplatinum ribbon having a length of 0.47 inches, a thickness of 0.0005inches, and a width of 0.040 inches. The electrodes 302 are adhesivelyconnected to one side of the silicone sheet 306.

The electrodes 302 are connected to a modified bipolar endocardialpacing lead, available under the trade name CONIFIX from Innomedica (nowBIOMEC Cardiovascular, Inc.), model number 501112. The proximal end ofthe cable 304 is connected to the control system 60 or driver 66 asdescribed previously. The pacing lead is modified by removing the pacingelectrode to form the cable body 304. The MP35 wires are extracted fromthe distal end thereof to form two coils 318 positioned side by sidehaving a diameter of about 0.020 inches. The coils 318 are then attachedto the electrodes utilizing 316 type stainless steel crimp terminalslaser welded to one end of the platinum electrodes 302. The distal endof the cable 304 and the connection between the coils 318 and the endsof the electrodes 302 are encapsulated by silicone.

The cable 304 illustrated in FIG. 14 comprises a coaxial type cableincluding two coaxially disposed coil leads separated into two separatecoils 318 for attachment to the electrodes 302. An alternative cable 304construction is illustrated in FIG. 15. FIG. 15 illustrates analternative cable body 304 which may be formed in a curvilinear shapesuch as a sinusoidal configuration, prior to implantation. Thecurvilinear configuration readily accommodates a change in distancebetween the device 300 and the control system 60 or the driver 66. Sucha change in distance may be encountered during flexion and/or extensionof the neck of the patient after implantation.

In this alternative embodiment, the cable body 304 may comprise two ormore conductive wires 304 a arranged coaxially or collinearly as shown.Each conductive wire 304 may comprise a multifilament structure ofsuitable conductive material such as stainless steel or MP35N. Aninsulating material may surround the wire conductors 304 a individuallyand/or collectively. For purposes of illustration only, a pair ofelectrically conductive wires 304 a having an insulating materialsurrounding each wire 304 a individually is shown. The insulated wires304 a may be connected by a spacer 304 b comprising, for example, aninsulating material. An additional jacket of suitable insulatingmaterial may surround each of the conductors 304 a. The insulatingjacket may be formed to have the same curvilinear shape of the insulatedwires 304 a to help maintain the shape of the cable body 304 duringimplantation.

If a sinusoidal configuration is chosen for the curvilinear shape, theamplitude (A) may range from 1 mm to 10 mm, and preferably ranges from 2mm to 3 mm. The wavelength (WL) of the sinusoid may range from 2 mm to20 mm, and preferably ranges from 4 mm to 10 mm. The curvilinear orsinusoidal shape may be formed by a heat setting procedure utilizing afixture which holds the cable 304 in the desired shape while the cableis exposed to heat. Sufficient heat is used to heat set the conductivewires 304 a and/or the surrounding insulating material. After cooling,the cable 304 may be removed from the fixture, and the cable 304 retainsthe desired shape.

Refer now to FIGS. 16-18 which illustrate various transducers that maybe mounted to the wall of a vessel such as a carotid artery 14 tomonitor wall expansion or contraction using strain, force and/orpressure gauges. An example of an implantable blood pressure measurementdevice that may be disposed about a blood vessel is disclosed in U.S.Pat. No. 6,106,477 to Miesel et al., the entire disclosure of which isincorporated herein by reference. The output from such gauges may becorrelated to blood pressure and/or heart rate, for example, and may beused to provide feedback to the control system 60 as describedpreviously herein. In FIG. 16, an implantable pressure measuringassembly comprises a foil strain gauge or force sensing resistor device740 disposed about an artery such as common carotid artery 14. Atransducer portion 742 may be mounted to a silicone base or backing 744which is wrapped around and sutured or otherwise attached to the artery14.

Alternatively, the transducer 750 may be adhesively connected to thewall of the artery 14 using a biologically compatible adhesive such ascyanoacrylate as shown in FIG. 17. In this embodiment, the transducer750 comprises a micro machined sensor (MEMS) that measures force orpressure. The MEMS transducer 750 includes a micro arm 752 (shown insection in FIG. 18) coupled to a silicon force sensor contained over anelastic base 754. A cap 756 covers the arm 752 a top portion of the base754. The base 754 include an interior opening creating access from thevessel wall 14 to the arm 752. An incompressible gel 756 fills the spacebetween the arm 752 and the vessel wall 14 such that force istransmitted to the arm upon expansion and contraction of the vesselwall. In both cases, changes in blood pressure within the artery causechanges in vessel wall stress which are detected by the transducer andwhich may be correlated with the blood pressure.

Refer now to FIGS. 19-21 which illustrate an alternative extravascularelectrical activation device 700, which, may also be referred to as anelectrode cuff device or more generally as an “electrode assembly.”Except as described herein and shown in the drawings, device 700 may bethe same in design and function as extravascular electrical activationdevice 300 described previously.

As seen in FIGS. 19 and 20, electrode assembly or cuff device 700includes coiled electrode conductors 702/704 embedded in a flexiblesupport 706. In the embodiment shown, an outer electrode coil 702 and aninner electrode coil 704 are used to provide a pseudo tripolararrangement, but other polar arrangements are applicable as well asdescribed previously. The coiled electrodes 702/704 may be formed offine round, flat or ellipsoidal wire such as 0.002 inch diameter roundPtIr alloy wire wound into a coil form having a nominal diameter of0.015 inches with a pitch of 0.004 inches, for example. The flexiblesupport or base 706 may be formed of a biocompatible and flexible(preferably elastic) material such as silicone or other suitable thinwalled elastomeric material having a wall thickness of 0.005 inches anda length (e.g., 2.95 inches) sufficient to surround the carotid sinus,for example.

Each turn of the coil in the contact area of the electrodes 702/704 isexposed from the flexible support 706 and any adhesive to form aconductive path to the artery wall. The exposed electrodes 702/704 mayhave a length (e.g., 0.236 inches) sufficient to extend around at leasta portion of the carotid sinus, for example. The electrode cuff 700 isassembled flat with the contact surfaces of the coil electrodes 702/704tangent to the inside plane of the flexible support 706. When theelectrode cuff 700 is wrapped around the artery, the inside contactsurfaces of the coiled electrodes 702/704 are naturally forced to extendslightly above the adjacent surface of the flexible support, therebyimproving contact to the artery wall.

The ratio of the diameter of the coiled electrodes 702/704 to the wirediameter is preferably large enough to allow the coil to bend andelongate without significant bending stress or torsional stress in thewire. Flexibility is a significant advantage of this design which allowsthe electrode cuff 700 to conform to the shape of the carotid artery andsinus, and permits expansion and contraction of the artery or sinuswithout encountering significant stress or fatigue. In particular, theflexible electrode cuff 700 may be wrapped around and stretched toconform to the shape of the carotid sinus and artery duringimplantation. This may be achieved without collapsing or distorting theshape of the artery and carotid sinus due to the compliance of theelectrode cuff 700. The flexible support 706 is able to flex and stretchwith the conductor coils 702/704 because of the absence of fabricreinforcement in the electrode contact portion of the cuff 700. Byconforming to the artery shape, and by the edge of the flexible support706 sealing against the artery wall, the amount of stray electricalfield and extraneous stimulation will likely be reduced.

The pitch of the coil electrodes 702/704 may be greater than the wirediameter in order to provide a space between each turn of the wire tothereby permit bending without necessarily requiring axial elongationthereof. For example, the pitch of the contact coils 702/704 may be0.004 inches per turn with a 0.002 inch diameter wire, which allows fora 0.002 inch space between the wires in each turn. The inside of thecoil may be filled with a flexible adhesive material such as siliconeadhesive which may fill the spaces between adjacent wire turns. Byfilling the small spaces between the adjacent coil turns, the chance ofpinching tissue between coil turns is minimized thereby avoidingabrasion to the artery wall. Thus, the embedded coil electrodes 702/704are mechanically captured and chemically bonded into the flexiblesupport 706. In the unlikely event that a coil electrode 702/704 comesloose from the support 706, the diameter of the coil is large enough tobe a traumatic to the artery wall. Preferably, the centerline of thecoil electrodes 702/704 lie near the neutral axis of electrode cuffstructure 700 and the flexible support 706 comprises a material withisotropic elasticity such as silicone in order to minimize the shearforces on the adhesive bonds between the coil electrodes 702/704 and thesupport 706.

The electrode coils 702/704 are connected to corresponding conductivecoils 712/714, respectively, in an elongate lead 710 which is connectedto the control system 60. Anchoring wings 718 may be provided on thelead 710 to tether the lead 710 to adjacent tissue and minimize theeffects or relative movement between the lead 710 and the electrode cuff700. As seen in FIG. 21, the conductive coils 712/714 may be formed of0.003 MP35N bifilar wires wound into 0.018 inch diameter coils which areelectrically connected to electrode coils 702/704 by splice wires 716.The conductive coils 712/714 may be individually covered by aninsulating covering 718 such as silicone tubing and collectively coveredby insulating covering 720.

The conductive material of the electrodes 702/704 may be a metal asdescribed above or a conductive polymer such as a silicone materialfilled with metallic particles such as Pt particles. In this latterembodiment, the polymeric electrodes may be integrally formed with theflexible support 706 with the electrode contacts comprising raised areason the inside surface of the flexible support 706 electrically coupledto the lead 710 by wires or wire coils. The use of polymeric electrodesmay be applied to other electrode design embodiments described elsewhereherein.

Reinforcement patches 708 such as DACRON® fabric may be selectivelyincorporated into the flexible support 706. For example, reinforcementpatches 708 may be incorporated into the ends or other areas of theflexible support 706 to accommodate suture anchors. The reinforcementpatches 708 provide points where the electrode cuff 700 may be suturedto the vessel wall and may also provide tissue in growth to furtheranchor the device 700 to the exterior of the vessel wall. For example,the fabric reinforcement patches 708 may extend beyond the edge of theflexible support 706 so that tissue in growth may help anchor theelectrode assembly or cuff 700 to the vessel wall and may reducereliance on the sutures to retain the electrode assembly 700 in place.As a substitute for or in addition to the sutures and tissue in growth,bioadhesives such as cyanoacrylate may be employed to secure the device700 to the vessel wall. In addition, an adhesive incorporatingconductive particles such as Pt coated micro spheres may be applied tothe exposed inside surfaces of the electrodes 702/704 to enhanceelectrical conduction to the tissue and possibly limit conduction alongone axis to limit extraneous tissue stimulation.

The reinforcement patches 708 may also be incorporated into the flexiblesupport 706 for strain relief purposes and to help retain the coils702/704 to the support 706 where the leads 710 attach to the electrodeassembly 700 as well as where the outer coil 702 loops back around theinner coil 704. Preferably, the patches 708 are selectively incorporatedinto the flexible support 706 to permit expansion and contraction of thedevice 700, particularly in the area of the electrodes 702/704. Inparticular, the flexible support 706 is only fabric reinforced inselected areas thereby maintaining the ability of the electrode cuff 700to stretch. Referring now to FIGS. 22-26, the electrode assembly ofFIGS. 19-21 can be modified to have “flattened” coil electrodes in theregion of the assembly where the electrodes contact the extravasculartissue. As shown in FIG. 22, an electrode-carrying surface 801 of theelectrode assembly, is located generally between parallel reinforcementstrips or tabs 808. The flattened coil section 810 will generally beexposed on a lower surface 803 of the base 806 (FIG. 23) and will becovered or encapsulated by a parylene or other polymeric structure ormaterial 802 over an upper surface 805 thereof. The coil is formed witha generally circular periphery 809, as best seen in FIGS. 24 and 26, andmay be mechanically flattened, typically over a silicone or othersupporting insert 815, as best seen in FIG. 25. The use of the flattenedcoil structure is particularly beneficial since it retains flexibility,allowing the electrodes to bend, stretch, and flex together with theelastomeric base 806, while also increasing the flat electrode areaavailable to contact the extravascular surface.

Referring now to FIGS. 27-30, an additional electrode assembly 900constructed in accordance with the principles of the present inventionwill be described. Electrode assembly 900 comprises an electrode base,typically an elastic base 902, typically formed from silicone or otherelastomeric material, having an electrode-carrying surface 904 and aplurality of attachment tabs 906 (906 a, 906 b, 906 c, and 906 d)extending from the electrode-carrying surface. The attachment tabs 906are preferably formed from the same material as the electrode-carryingsurface 904 of the base 902, but could be formed from other elastomericmaterials as well. In the latter case, the base will be molded,stretched or otherwise assembled from the various pieces. In theillustrated embodiment, the attachment tabs 906 are formed integrallywith the remainder of the base 902, i.e., typically being cut from asingle sheet of the elastomeric material.

The geometry of the electrode assembly 900, and in particular thegeometry of the base 902, is selected to permit a number of differentattachment modes to the blood vessel. In particular, the geometry of theassembly 902 of FIG. 27 is intended to permit attachment to variouslocations on the carotid arteries at or near the carotid sinus andcarotid bifurcation.

A number of reinforcement regions 910 (910 a, 910 b, 910 c, 910 d, and910 e) are attached to different locations on the base 902 to permitsuturing, clipping, stapling, or other fastening of the attachment tabs906 to each other and/or the electrode-carrying surface 904 of the base902. In the preferred embodiment intended for attachment at or aroundthe carotid sinus, a first reinforcement strip 910 a is provided over anend of the base 902 opposite to the end which carries the attachmenttabs. Pairs of reinforcement strips 910 b and 910 c are provided on eachof the axially aligned attachment tabs 906 a and 906 b, while similarpairs of reinforcement strips 910 d and 910 e are provided on each ofthe transversely angled attachment tabs 906 c and 906 d. In theillustrated embodiment, all attachment tabs will be provided on one sideof the base, preferably emanating from adjacent corners of therectangular electrode-carrying surface 904.

The structure of electrode assembly 900 permits the surgeon to implantthe electrode assembly so that the electrodes 920 (which are preferablystretchable, flat-coil electrodes as described in detail above), arelocated at a preferred location relative to the target baroreceptors.The preferred location may be determined, for example, as described incommonly assigned U.S. Pat. No. 6,985,774, the full disclosure of whichincorporated herein by reference.

Once the preferred location for the electrodes 920 of the electrodeassembly 900 is determined, the surgeon may position the base 902 sothat the electrodes 920 are located appropriately relative to theunderlying baroreceptors. Thus, the electrodes 920 may be positionedover the common carotid artery CC as shown in FIG. 28, or over theinternal carotid artery IC, as shown in FIGS. 29 and 30. In FIG. 28, theassembly 900 may be attached by stretching the base 902 and attachmenttabs 906 a and 906 b over the exterior of the common carotid artery. Thereinforcement tabs 906 a or 906 b may then be secured to thereinforcement strip 910 a, either by suturing, stapling, fastening,gluing, welding, or other well-known means. Usually, the reinforcementtabs 906 c and 906 d will be cut off at their bases, as shown at 922 and924, respectively.

In other cases, the bulge of the carotid sinus and the baroreceptors maybe located differently with respect to the carotid bifurcation. Forexample, as shown in FIG. 29, the receptors may be located further upthe internal carotid artery IC so that the placement of electrodeassembly 900 as shown in FIG. 28 will not work. The assembly 900,however, may still be successfully attached by utilizing thetransversely angled attachment tabs 906 c and 906 d rather than thecentral or axial tabs 906 a and 906 b. As shown in FIG. 29, the lowertab 906 d is wrapped around the common carotid artery CC, while theupper attachment tab 906 c is wrapped around the internal carotid arteryIC. The axial attachment tabs 906 a and 906 b will usually be cut off(at locations 926), although neither of them could in some instancesalso be wrapped around the internal carotid artery IC. Again, the tabswhich are used may be stretched and attached to reinforcement strip 910a, as generally described above.

Referring to FIG. 30, in instances where the carotid bifurcation hasless of an angle, the assembly 900 may be attached using the upper axialattachment tab 906 a and be lower transversely angled attachment tab 906d. Attachment tabs 906 b and 906 c may be cut off, as shown at locations928 and 930, respectively. In all instances, the elastic nature of thebase 902 and the stretchable nature of the electrodes 920 permit thedesired conformance and secure mounting of the electrode assembly overthe carotid sinus. It would be appreciated that these or similarstructures would also be useful for mounting electrode structures atother locations in the vascular system.

Refer now to FIGS. 32A and 32B which show schematic illustrations of abaroreceptor activation device 100 in the form of an intravascularinflatable balloon. The inflatable balloon device 100 includes a helicalballoon 102 which is connected to a fluid line 104. An example of asimilar helical balloon is disclosed in U.S. Pat. No. 5,181,911 toShturman, the entire disclosure of which is hereby incorporated byreference. The balloon 102 preferably has a helical geometry or anyother geometry which allows blood perfusion therethrough. The fluid line104 is connected to the driver 66 of the control system 60. In thisembodiment, the driver 66 comprises a pressure/vacuum source (i.e., aninflation device) which selectively inflates and deflates the helicalballoon 102. Upon inflation, the helical balloon 102 expands, preferablyincreasing in outside diameter only, to mechanically activatebaroreceptors 30 by stretching or otherwise deforming them and/or thevascular wall 40. Upon deflation, the helical balloon 102 returns to itsrelaxed geometry such that the vascular wall 40 returns to its nominalstate. Thus, by selectively inflating the helical balloon 102, thebaroreceptors 30 adjacent thereto may be selectively activated.

As an alternative to pneumatic or hydraulic expansion utilizing aballoon, a mechanical expansion device (not shown) may be used to expandor dilate the vascular wall 40 and thereby mechanically activate thebaroreceptors 30. For example, the mechanical expansion device maycomprise a tubular wire braid structure that diametrically expands whenlongitudinally compressed as disclosed in U.S. Pat. No. 5,222,971 toWillard et al., the entire disclosure of which is hereby incorporated byreference. The tubular braid may be disposed intravascularly and permitsblood perfusion through the wire mesh. In this embodiment, the driver 66may comprise a linear actuator connected by actuation cables to oppositeends of the braid. When the opposite ends of the tubular braid arebrought closer together by actuation of the cables, the diameter of thebraid increases to expand the vascular wall 40 and activate thebaroreceptors 30.

Refer now to FIGS. 33A and 33B which show schematic illustrations of abaroreceptor activation device 120 in the form of an extravascularpressure cuff. The pressure cuff device 120 includes an inflatable cuff122 which is connected to a fluid line 124. Examples of a similar cuffs122 are disclosed in U.S. Pat. No. 4,256,094 to Kapp et al. and U.S.Pat. No. 4,881,939 to Newman, the entire disclosures of which are herebyincorporated by reference. The fluid line 124 is connected to the driver66 of the control system 60. In this embodiment, the driver 66 comprisesa pressure/vacuum source (i.e., an inflation device) which selectivelyinflates and deflates the cuff 122. Upon inflation, the cuff 122expands, preferably increasing in inside diameter only, to mechanicallyactivate baroreceptors 30 by stretching or otherwise deforming themand/or the vascular wall 40. Upon deflation, the cuff 122 returns to itsrelaxed geometry such that the vascular wall 40 returns to its nominalstate. Thus, by selectively inflating the inflatable cuff 122, thebaroreceptors 30 adjacent thereto may be selectively activated.

The driver 66 may be automatically actuated by the control system 60 asdiscussed above, or may be manually actuated. An example of anexternally manually actuated pressure/vacuum source is disclosed in U.S.Pat. No. 4,709,690 to Haber, the entire disclosure of which is herebyincorporated by reference. Examples of transdermally manually actuatedpressure/vacuum sources are disclosed in U.S. Pat. No. 4,586,501 toClaracq, U.S. Pat. No. 4,828,544 to Lane et al., and U.S. Pat. No.5,634,878 to Grundei et al., the entire disclosures of which are herebyincorporated by reference.

Those skilled in the art will recognize that other external compressiondevices may be used in place of the inflatable cuff device 120. Forexample, a piston actuated by a solenoid may apply compression to thevascular wall. An example of a solenoid actuated piston device isdisclosed in U.S. Pat. No. 4,014,318 to Dokum et al, and an example of ahydraulically or pneumatically actuated piston device is disclosed inU.S. Pat. No. 4,586,501 to Claracq, the entire disclosures of which arehereby incorporated by reference. Other examples include a rotary ringcompression device as disclosed in U.S. Pat. No. 4,551,862 to Haber, andan electromagnetically actuated compression ring device as disclosed inU.S. Pat. No. 5,509,888 to Miller, the entire disclosures of which arehereby incorporated by reference.

Refer now to FIGS. 34A and 34B which show schematic illustrations of abaroreceptor activation device 140 in the form of an intravasculardeformable structure. The deformable structure device 140 includes acoil, braid or other stent-like structure 142 disposed in the vascularlumen. The deformable structure 142 includes one or more individualstructural members connected to an electrical lead 144. Each of thestructural members forming deformable structure 142 may comprise a shapememory material 146 (e.g., nickel titanium alloy) as illustrated in FIG.34C, or a bimetallic material 148 as illustrated in FIG. 34D. Theelectrical lead 144 is connected to the driver 66 of the control system60. In this embodiment, the driver 66 comprises an electric powergenerator or amplifier which selectively delivers electric current tothe structure 142 which resistively heats the structural members146/148. The structure 142 may be unipolar as shown using thesurrounding tissue as ground, or bipolar or multipolar using leadsconnected to either end of the structure 142. Electrical power may alsobe delivered to the structure 142 inductively as described hereinafterwith reference to FIGS. 41A-43B.

Upon application of electrical current to the shape memory material 146,it is resistively heated causing a phase change and a correspondingchange in shape. Upon application of electrical current to thebimetallic material 148, it is resistively heated causing a differentialin thermal expansion and a corresponding change in shape. In eithercase, the material 146/148 is designed such that the change in shapecauses expansion of the structure 142 to mechanically activatebaroreceptors 30 by stretching or otherwise deforming them and/or thevascular wall 40. Upon removal of the electrical current, the material146/148 cools and the structure 142 returns to its relaxed geometry suchthat the baroreceptors 30 and/or the vascular wall 40 return to theirnominal state. Thus, by selectively expanding the structure 142, thebaroreceptors 30 adjacent thereto may be selectively activated.

Refer now to FIGS. 35A and 35B which show schematic illustrations of abaroreceptor activation device 160 in the form of an extravasculardeformable structure. The extravascular deformable structure device 160is substantially the same as the intravascular deformable structuredevice 140 described with reference to FIGS. 34A and 34B, except thatthe extravascular device 160 is disposed about the vascular wall, andtherefore compresses, rather than expands, the vascular wall 40. Thedeformable structure device 160 includes a coil, braid or otherstent-like structure 162 comprising one or more individual structuralmembers connected to an electrical lead 164. Each of the structuralmembers may comprise a shape memory material 166 (e.g., nickel titaniumalloy) as illustrated in FIG. 35C, or a bimetallic material 168 asillustrated in FIG. 35D. The structure 162 may be unipolar as shownusing the surrounding tissue as ground, or bipolar or multipolar usingleads connected to either end of the structure 162. Electrical power mayalso be delivered to the structure 162 inductively as describedhereinafter with reference to FIGS. 41A-43B.

Upon application of electrical current to the shape memory material 166,it is resistively heated causing a phase change and a correspondingchange in shape. Upon application of electrical current to thebimetallic material 168, it is resistively heated causing a differentialin thermal expansion and a corresponding change in shape. In eithercase, the material 166/168 is designed such that the change in shapecauses constriction of the structure 162 to mechanically activatebaroreceptors 30 by compressing or otherwise deforming the baroreceptors30 and/or the vascular wall 40. Upon removal of the electrical current,the material 166/168 cools and the structure 162 returns to its relaxedgeometry such that the baroreceptors 30 and/or the vascular wall 40return to their nominal state. Thus, by selectively compressing thestructure 162, the baroreceptors 30 adjacent thereto may be selectivelyactivated.

Refer now to FIGS. 36A and 36B which show schematic illustrations of abaroreceptor activation device 180 in the form of an extravascular flowregulator which artificially creates back pressure adjacent thebaroreceptors 30. The flow regulator device 180 includes an externalcompression device 182, which may comprise any of the externalcompression devices described with reference to FIGS. 33A and 33B. Theexternal compression device 182 is operably connected to the driver 66of the control system 60 by way of cable 184, which may comprise a fluidline or electrical lead, depending on the type of external compressiondevice 182 utilized. The external compression device 182 is disposedabout the vascular wall distal of the baroreceptors 30. For example, theexternal compression device 182 may be located in the distal portions ofthe external or internal carotid arteries 18/19 to create back pressureadjacent to the baroreceptors 30 in the carotid sinus region 20.Alternatively, the external compression device 182 may be located in theright subclavian artery 13, the right common carotid artery 14, the leftcommon carotid artery 15, the left subclavian artery 16, or thebrachiocephalic artery 22 to create back pressure adjacent thebaroreceptors 30 in the aortic arch 12.

Upon actuation of the external compression device 182, the vascular wallis constricted thereby reducing the size of the vascular lumen therein.By reducing the size of the vascular lumen, pressure proximal of theexternal compression device 182 is increased thereby expanding thevascular wall. Thus, by selectively activating the external compressiondevice 182 to constrict the vascular lumen and create back pressure, thebaroreceptors 30 may be selectively activated.

Refer now to FIGS. 37A and 37B which show schematic illustrations of abaroreceptor activation device 200 in the form of an intravascular flowregular which artificially creates back pressure adjacent thebaroreceptors 30. The intravascular flow regulator device 200 issubstantially similar in function and use as extravascular flowregulator 180 described with reference to FIGS. 36A and 36B, except thatthe intravascular flow regulator device 200 is disposed in the vascularlumen.

Intravascular flow regulator 200 includes an internal valve 202 to atleast partially close the vascular lumen distal of the baroreceptors 30.By at least partially closing the vascular lumen distal of thebaroreceptors 30, back pressure is created proximal of the internalvalve 202 such that the vascular wall expands to activate thebaroreceptors 30. The internal valve 202 may be positioned at any of thelocations described with reference to the external compression device182, except that the internal valve 202 is placed within the vascularlumen. Specifically, the internal compression device 202 may be locatedin the distal portions of the external or internal carotid arteries18/19 to create back pressure adjacent to the baroreceptors 30 in thecarotid sinus region 20. Alternatively, the internal compression device202 may be located in the right subclavian artery 13, the right commoncarotid artery 14, the left common carotid artery 15, the leftsubclavian artery 16, or the brachiocephalic artery 22 to create backpressure adjacent the baroreceptors 30 in the aortic arch 12.

The internal valve 202 is operably coupled to the driver 66 of thecontrol system 60 by way of electrical lead 204. The control system 60may selectively open, close or change the flow resistance of the valve202 as described in more detail hereinafter. The internal valve 202 mayinclude valve leaflets 206 (bi-leaflet or tri-leaflet) which rotateinside housing 208 about an axis between an open position and a closedposition. The closed position may be completely closed or partiallyclosed, depending on the desired amount of back pressure to be created.The opening and closing of the internal valve 202 may be selectivelycontrolled by altering the resistance of leaflet 206 rotation or byaltering the opening force of the leaflets 206. The resistance ofrotation of the leaflets 206 may be altered utilizingelectromagnetically actuated metallic bearings carried by the housing208. The opening force of the leaflets 206 may be altered by utilizingelectromagnetic coils in each of the leaflets to selectively magnetizethe leaflets such that they either repel or attract each other, therebyfacilitating valve opening and closing, respectively.

A wide variety of intravascular flow regulators may be used in place ofinternal valve 202. For example, internal inflatable balloon devices asdisclosed in U.S. Pat. No. 4,682,583 to Burton et al. and U.S. Pat. No.5,634,878 to Grundei et al., the entire disclosures of which is herebyincorporated by reference, may be adapted for use in place of valve 202.Such inflatable balloon device, may be operated in a similar manner asthe inflatable cuff 122 described with reference to FIG. 33.Specifically, in this embodiment, the driver 66 would comprises apressure/vacuum source (i.e., an inflation device) which selectivelyinflates and deflates the internal balloon. Upon inflation, the balloonexpands to partially occlude blood flow and create back pressure tomechanically activate baroreceptors 30 by stretching or otherwisedeforming them and/or the vascular wall 40. Upon deflation, the internalballoon returns to its normal profile such that flow is not hindered andback pressure is eliminated. Thus, by selectively inflating the internalballoon, the baroreceptors 30 proximal thereof may be selectivelyactivated by creating back pressure.

Refer now to FIGS. 38A and 38B which show schematic illustrations of abaroreceptor activation device 220 in the form of magnetic particles 222disposed in the vascular wall 40. The magnetic particles 222 maycomprise magnetically responsive materials (i.e., ferrous basedmaterials) and may be magnetically neutral or magnetically active.Preferably, the magnetic particles 222 comprise permanent magnets havingan elongate cylinder shape with north and south poles to stronglyrespond to magnetic fields. The magnetic particles 222 are actuated byan electromagnetic coil 224 which is operably coupled to the driver 66of the control system 60 by way of an electrical cable 226. Theelectromagnetic coil 224 may be implanted as shown, or located outsidethe body, in which case the driver 66 and the remainder of the controlsystem 60 would also be located outside the body. By selectivelyactivating the electromagnetic coil 224 to create a magnetic field, themagnetic particles 222 may be repelled, attracted or rotated.Alternatively, the magnetic field created by the electromagnetic coil224 may be alternated such that the magnetic particles 222 vibratewithin the vascular wall 40. When the magnetic particles are repelled,attracted, rotated, vibrated or otherwise moved by the magnetic fieldcreated by the electromagnetic coil 224, the baroreceptors 30 aremechanically activated.

The electromagnetic coil 224 is preferably placed as close as possibleto the magnetic particles 222 in the vascular wall 40, and may be placedintravascularly, extravascularly, or in any of the alternative locationsdiscussed with reference to inductor shown in FIGS. 41A-43B. Themagnetic particles 222 may be implanted in the vascular wall 40 byinjecting a ferro-fluid or a ferro-particle suspension into the vascularwall adjacent to the baroreceptors 30. To increase biocompatibility, theparticles 222 may be coated with a ceramic, polymeric or other inertmaterial. Injection of the fluid carrying the magnetic particles 222 ispreferably performed percutaneously.

Refer now to FIGS. 39A and 39B which show schematic illustrations of abaroreceptor activation device 240 in the form of one or moretransducers 242. Preferably, the transducers 242 comprise an arraysurrounding the vascular wall. The transducers 242 may beintravascularly or extravascularly positioned adjacent to thebaroreceptors 30. In this embodiment, the transducers 242 comprisedevices which convert electrical signals into some physical phenomena,such as mechanical vibration or acoustic waves. The electrical signalsare provided to the transducers 242 by way of electrical cables 244which are connected to the driver 66 of the control system 60. Byselectively activating the transducers 242 to create a physicalphenomena, the baroreceptors 30 may be mechanically activated.

The transducers 242 may comprise an acoustic transmitter which transmitssonic or ultrasonic sound waves into the vascular wall 40 to activatethe baroreceptors 30. Alternatively, the transducers 242 may comprise apiezoelectric material which vibrates the vascular wall to activate thebaroreceptors 30. As a further alternative, the transducers 242 maycomprise an artificial muscle which deflects upon application of anelectrical signal. An example of an artificial muscle transducercomprises plastic impregnated with a lithium-perchlorate electrolytedisposed between sheets of polypyrrole, a conductive polymer. Suchplastic muscles may be electrically activated to cause deflection indifferent directions depending on the polarity of the applied current.

Refer now to FIGS. 31A and 31B which show schematic illustrations of abaroreceptor activation device 260 in the form of a local fluid deliverydevice 262 suitable for delivering a chemical or biological fluid agentto the vascular wall adjacent the baroreceptors 30. The local fluiddelivery device 262 may be located intravascularly, extravascularly, orintramurally. For purposes of illustration only, the local fluiddelivery device 262 is positioned extravascularly.

The local fluid delivery device 262 may include proximal and distalseals 266 which retain the fluid agent disposed in the lumen or cavity268 adjacent to vascular wall. Preferably, the local fluid deliverydevice 262 completely surrounds the vascular wall 40 to maintain aneffective seal. Those skilled in the art will recognize that the localfluid delivery device 262 may comprise a wide variety of implantabledrug delivery devices or pumps known in the art.

The local fluid delivery device 260 is connected to a fluid line 264which is connected to the driver 66 of the control system 60. In thisembodiment, the driver 66 comprises a pressure/vacuum source and fluidreservoir containing the desired chemical or biological fluid agent. Thechemical or biological fluid agent may comprise a wide variety ofstimulatory substances. Examples include veratridine, bradykinin,prostaglandins, and related substances. Such stimulatory substancesactivate the baroreceptors 30 directly or enhance their sensitivity toother stimuli and therefore may be used in combination with the otherbaroreceptor activation devices described herein. Other examples includegrowth factors and other agents that modify the function of thebaroreceptors 30 or the cells of the vascular tissue surrounding thebaroreceptors 30 causing the baroreceptors 30 to be activated or causingalteration of their responsiveness or activation pattern to otherstimuli.

Refer now to FIGS. 40A and 40B which show schematic illustrations of abaroreceptor activation device 280 in the form of an intravascularelectrically conductive structure or electrode 282. The electrodestructure 282 may comprise a self-expanding or balloon expandable coil,braid or other stent-like structure disposed in the vascular lumen. Theelectrode structure 282 may serve the dual purpose of maintaining lumenpatency while also delivering electrical stimuli. To this end, theelectrode structure 282 may be implanted utilizing conventionalintravascular stent and filter delivery techniques. Preferably, theelectrode structure 282 comprises a geometry which allows bloodperfusion therethrough. The electrode structure 282 compriseselectrically conductive material which may be selectively insulated toestablish contact with the inside surface of the vascular wall 40 atdesired locations, and limit extraneous electrical contact with bloodflowing through the vessel and other tissues.

The electrode structure 282 is connected to electric lead 284 which isconnected to the driver 66 of the control system 60. The driver 66, inthis embodiment, may comprise a power amplifier, pulse generator or thelike to selectively deliver electrical control signals to structure 282.As mentioned previously, the electrical control signal generated by thedriver 66 may be continuous, periodic, episodic or a combinationthereof, as dictated by an algorithm contained in memory 62 of thecontrol system 60. Continuous control signals include a constant pulse,a constant train of pulses, a triggered pulse and a triggered train ofpulses. Periodic control signals include each of the continuous controlsignals described above which have a designated start time and adesignated duration. Episodic control signals include each of thecontinuous control signals described above which are triggered by anepisode.

By selectively activating, deactivating or otherwise modulating theelectrical control signal transmitted to the electrode structure 282,electrical energy may be delivered to the vascular wall to activate thebaroreceptors 30. As discussed previously, activation of thebaroreceptors 30 may occur directly or indirectly. In particular, theelectrical signal delivered to the vascular wall 40 by the electrodestructure 282 may cause the vascular wall to stretch or otherwise deformthereby indirectly activating the baroreceptors 30 disposed therein.Alternatively, the electrical signals delivered to the vascular wall bythe electrode structure 282 may directly activate the baroreceptors 30by changing the electrical potential across the baroreceptors 30. Ineither case, the electrical signal is delivered to the vascular wall 40immediately adjacent to the baroreceptors 30. It is also contemplatedthat the electrode structure 282 may delivery thermal energy byutilizing a semi-conductive material having a higher resistance suchthat the electrode structure 282 resistively generates heat uponapplication of electrical energy.

Various alternative embodiments are contemplated for the electrodestructure 282, including its design, implanted location, and method ofelectrical activation. For example, the electrode structure 282 may beunipolar as shown in FIGS. 40A and 40B using the surrounding tissue asground, or bipolar using leads connected to either end of the structure282 as shown in FIGS. 44A and 44B. In the embodiment of FIGS. 44A and4B, the electrode structure 282 includes two or more individualelectrically conductive members 283/285 which are electrically isolatedat their respective cross-over points utilizing insulative materials.Each of the members 283/285 is connected to a separate conductorcontained within the electrical lead 284. Alternatively, an array ofbipoles may be used as described in more detail with reference to FIG.47. As a further alternative, a multipolar arrangement may be usedwherein three or more electrically conductive members are included inthe structure 282. For example, a tripolar arrangement may be providedby one electrically conductive member having a polarity disposed betweentwo electrically conductive members having the opposite polarity.

In terms of electrical activation, the electrical signals may bedirectly delivered to the electrode structure 282 as described withreference to FIGS. 40A and 40B, or indirectly delivered utilizing aninductor as illustrated in FIGS. 41A-43A and 47. The embodiments ofFIGS. 41A-43A and 47 utilize an inductor 286 which is operably connectedto the driver 66 of the control system 60 by way of electrical lead 284.The inductor 286 comprises an electrical winding which creates amagnetic field 287 (as seen in FIG. 47) around the electrode structure282. The magnetic field 287 may be alternated by alternating thedirection of current flow through the inductor 286. Accordingly, theinductor 286 may be utilized to create current flow in the electrodestructure 282 to thereby deliver electrical signals to the vascular wall40 to directly or indirectly activate the baroreceptors 30. In allembodiments, the inductor 286 may be covered with an electricallyinsulative material to eliminate direct electrical stimulation oftissues surrounding the inductor 286. A preferred embodiment of aninductively activated electrode structure 282 is described in moredetail with reference to FIGS. 47A-47C.

The embodiments of FIGS. 40-43 may be modified to form a cathode/anodearrangement. Specifically, the electrical inductor 286 would beconnected to the driver 66 as shown in FIGS. 41-43 and the electrodestructure 282 would be connected to the driver 66 as shown in FIG. 40.With this arrangement, the electrode structure 282 and the inductor 286may be any suitable geometry and need not be coiled for purposes ofinduction. The electrode structure 282 and the inductor 286 wouldcomprise a cathode/anode or anode/cathode pair. For example, whenactivated, the cathode 282 may generate a primary stream of electronswhich travel through the inter-electrode space (i.e., vascular tissueand baroreceptors 30) to the anode 286. The cathode is preferably cold,as opposed to thermionic, during electron emission. The electrons may beused to electrically or thermally activate the baroreceptors 30 asdiscussed previously.

The electrical inductor 286 is preferably disposed as close as possibleto the electrode structure 282. For example, the electrical inductor 286may be disposed adjacent the vascular wall as illustrated in FIGS. 41Aand 41B. Alternatively, the inductor 286 may be disposed in an adjacentvessel as illustrated in FIGS. 42A and 42B. If the electrode structure282 is disposed in the carotid sinus 20, for example, the inductor 286may be disposed in the internal jugular vein 21 as illustrated in FIGS.42A and 42B. In the embodiment of FIGS. 42A and 42B, the electricalinductor 286 may comprise a similar structure as the electrode structure282. As a further alternative, the electrical inductor 286 may bedisposed outside the patient's body, but as close as possible to theelectrode structure 282. If the electrode structure 282 is disposed inthe carotid sinus 20, for example, the electrical inductor 286 may bedisposed on the right or left side of the neck of the patient asillustrated in FIGS. 43A and 43B. In the embodiment of FIGS. 43A and43B, wherein the electrical inductor 286 is disposed outside thepatient's body, the control system 60 may also be disposed outside thepatient's body.

In terms of implant location, the electrode structure 282 may beintravascularly disposed as described with reference to FIGS. 40A and40B, or extravascularly disposed as described with reference to FIGS. 4Aand 4B, which show schematic illustrations of a baroreceptor activationdevice 300 in the form of an extravascular electrically conductivestructure or electrode 302. Except as described herein, theextravascular electrode structure 302 is the same in design, function,and use as the intravascular electrode structure 282. The electrodestructure 302 may comprise a coil, braid or other structure capable ofsurrounding the vascular wall. Alternatively, the electrode structure302 may comprise one or more electrode patches distributed around theoutside surface of the vascular wall. Because the electrode structure302 is disposed on the outside surface of the vascular wall,intravascular delivery techniques may not be practical, but minimallyinvasive surgical techniques will suffice. The extravascular electrodestructure 302 may receive electrical signals directly from the driver 66of the control system 60 by way of electrical lead 304, or indirectly byutilizing an inductor (not shown) as described with reference to FIGS.41-43 and in commonly assigned U.S. Pat. No. 7,616,997, the fulldisclosure of which is incorporated herein by reference.

Refer now to FIGS. 45A and 45B which show schematic illustrations of abaroreceptor activation device 320 in the form of electricallyconductive particles 322 disposed in the vascular wall. This embodimentis substantially the same as the embodiments described with reference toFIGS. 4 and 40-44, except that the electrically conductive particles 322are disposed within the vascular wall, as opposed to the electricallyconductive structures 282/302 which are disposed on either side of thevascular wall. In addition, this embodiment is similar to the embodimentdescribed with reference to FIG. 38, except that the electricallyconductive particles 322 are not necessarily magnetic as with magneticparticles 222, and the electrically conductive particles 322 are drivenby an electromagnetic field rather than by a magnetic field.

In this embodiment, the driver 66 of the control system 60 comprises anelectromagnetic transmitter such as an radiofrequency or microwavetransmitter. Electromagnetic radiation is created by the transmitter 66which is operably coupled to an antenna 324 by way of electrical lead326. Electromagnetic waves are emitted by the antenna 324 and receivedby the electrically conductive particles 322 disposed in the vascularwall 40. Electromagnetic energy creates oscillating current flow withinthe electrically conductive particles 322, and depending on theintensity of the electromagnetic radiation and the resistivity of theconductive particles 322, may cause the electrical particles 322 togenerate heat. The electrical or thermal energy generated by theelectrically conductive particles 322 may directly activate thebaroreceptors 30, or indirectly activate the baroreceptors 30 by way ofthe surrounding vascular wall tissue.

The electromagnetic radiation transmitter 66 and antenna 324 may bedisposed in the patient's body, with the antenna 324 disposed adjacentto the conductive particles in the vascular wall 40 as illustrated inFIGS. 45A and 45B. Alternatively, the antenna 324 may be disposed in anyof the positions described with reference to the electrical inductorshown in FIGS. 41-43. It is also contemplated that the electromagneticradiation transmitter 66 and antenna 324 may be utilized in combinationwith the intravascular and extravascular electrically conductivestructures 282/302 described with reference to FIGS. 4 and 40-44 togenerate thermal energy on either side of the vascular wall.

As an alternative, the electromagnetic radiation transmitter 66 andantenna 324 may be used without the electrically conductive particles322. Specifically, the electromagnetic radiation transmitter 66 andantenna 324 may be used to deliver electromagnetic radiation (e.g., RF,microwave) directly to the baroreceptors 30 or the tissue adjacentthereto to cause localized heating, thereby thermally inducing abaroreceptor 30 signal.

Refer now to FIGS. 46A and 46B which show schematic illustrations of abaroreceptor activation device 340 in the form of a Peltier effectdevice 342. The Peltier effect device 342 may be extravascularlypositioned as illustrated, or may be intravascularly positioned similarto an intravascular stent or filter. The Peltier effect device 342 isoperably connected to the driver 66 of the control system 60 by way ofelectrical lead 344. The Peltier effect device 342 includes twodissimilar metals or semiconductors 343/345 separated by a thermaltransfer junction 347. In this particular embodiment, the driver 66comprises a power source which delivers electrical energy to thedissimilar metals or semiconductors 343/345 to create current flowacross the thermal junction 347.

When current is delivered in an appropriate direction, a cooling effectis created at the thermal junction 347. There is also a heating effectcreated at the junction between the individual leads 344 connected tothe dissimilar metals or semiconductors 343/345. This heating effect,which is proportional to the cooling effect, may be utilized to activatethe baroreceptors 30 by positioning the junction between the electricalleads 344 and the dissimilar metals or semiconductors 343/345 adjacentto the vascular wall 40.

Refer now to FIGS. 47A-47C which show schematic illustrations of apreferred embodiment of an inductively activated electrode structure 282for use with the embodiments described with reference to FIGS. 41-43. Inthis embodiment, current flow in the electrode structure 282 is inducedby a magnetic field 287 created by an inductor 286 which is operablycoupled to the driver 66 of the control system 60 by way of electricalcable 284. The electrode structure 282 preferably comprises amulti-filar self-expanding braid structure including a plurality ofindividual members 282 a, 282 b, 282 c and 282 d. However, the electrodestructure 282 may simply comprise a single coil for purposes of thisembodiment.

Each of the individual coil members 282 a-282 d comprising the electrodestructure 282 consists of a plurality of individual coil turns 281connected end to end as illustrated in FIGS. 47B and 47C. FIG. 47C is adetailed view of the connection between adjacent coil turns 281 as shownin FIG. 47B. Each coil turn 281 comprises electrically isolated wires orreceivers in which a current flow is established when a changingmagnetic field 287 is created by the inductor 286. The inductor 286 ispreferably covered with an electrically insulative material to eliminatedirect electrical stimulation of tissues surrounding the inductor 286.Current flow through each coil turn 281 results in a potential drop 288between each end of the coil turn 281. With a potential drop defined ateach junction between adjacent coil turns 281, a localized current flowcell is created in the vessel wall adjacent each junction. Thus an arrayor plurality of bipoles are created by the electrode structure 282 anduniformly distributed around the vessel wall. Each coil turn 281comprises an electrically conductive wire material 290 surrounded by anelectrically insulative material 292. The ends of each coil turn 281 areconnected by an electrically insulated material 294 such that each coilturn 281 remains electrically isolated. The insulative material 294mechanically joins but electrically isolates adjacent coil turns 281such that each turn 281 responds with a similar potential drop 288 whencurrent flow is induced by the changing magnetic field 287 of theinductor 286. An exposed portion 296 is provided at each end of eachcoil turn 281 to facilitate contact with the vascular wall tissue. Eachexposed portion 296 comprises an isolated electrode in contact with thevessel wall. The changing magnetic field 287 of the inductor 286 causesa potential drop in each coil turn 281 thereby creating small currentflow cells in the vessel wall corresponding to adjacent exposed regions296. The creation of multiple small current cells along the inner wallof the blood vessel serves to create a cylindrical zone of relativelyhigh current density such that the baroreceptors 30 are activated.However, the cylindrical current density field quickly reduces to anegligible current density near the outer wall of the vascular wall,which serves to limit extraneous current leakage to minimize oreliminate unwanted activation of extravascular tissues and structuressuch as nerves or muscles.

To address low blood pressure and other conditions requiring bloodpressure augmentation, some of the baroreceptor activation devicesdescribed previously may be used to selectively and controllablyregulate blood pressure by inhibiting or dampening baroreceptor signals.By selectively and controllably inhibiting or dampening baroreceptorsignals, the present invention reduces conditions associated with lowblood pressure as described previously. Specifically, the presentinvention would function to increase the blood pressure and level ofsympathetic nervous system activation by inhibiting or dampening theactivation of baroreceptors.

This may be accomplished by utilizing mechanical, thermal, electricaland chemical or biological means. Mechanical means may be triggered offthe pressure pulse of the heart to mechanically limit deformation of thearterial wall. For example, either of the external compression devices120/160 described previously may be used to limit deformation of thearterial wall. Alternatively, the external compression device may simplylimit diametrical expansion of the vascular wall adjacent thebaroreceptors without the need for a trigger or control signal.

Thermal means may be used to cool the baroreceptors 30 and adjacenttissue to reduce the responsiveness of the baroreceptors 30 and therebydampen baroreceptor signals. Specifically, the baroreceptor 30 signalsmay be dampened by either directly cooling the baroreceptors 30, toreduce their sensitivity, metabolic activity and function, or by coolingthe surrounding vascular wall tissue thereby causing the wall to becomeless responsive to increases in blood pressure. An example of thisapproach is to use the cooling effect of the Peltier device 340.Specifically, the thermal transfer junction 347 may be positionedadjacent the vascular wall to provide a cooling effect. The coolingeffect may be used to dampen signals generated by the baroreceptors 30.Another example of this approach is to use the fluid delivery device 260to deliver a cool or cold fluid (e.g. saline). In this embodiment, thedriver 66 would include a heat exchanger to cool the fluid and thecontrol system 60 may be used to regulate the temperature of the fluid,thereby regulating the degree of baroreceptor 30 signal dampening.

Electrical means may be used to inhibit baroreceptor 30 activation by,for example, hyperpolarizing cells in or adjacent to the baroreceptors30. Examples of devices and method of hyperpolarizing cells aredisclosed in U.S. Pat. No. 5,814,079 to Kieval, and U.S. Pat. No.5,800,464 to Kieval, the entire disclosures of which are herebyincorporated by reference. Such electrical means may be implementedusing any of the embodiments discussed with reference to FIGS. 4, 40-44and 47.

Chemical or biological means may be used to reduce the sensitivity ofthe baroreceptors 30. For example, a substance that reduces baroreceptorsensitivity may be delivered using the fluid delivery device 260described previously. The desensitizing agent may comprise, for example,tetrodotoxin or other inhibitor of excitable tissues. From theforegoing, it should be apparent to those skilled in the art that thepresent invention provides a number of devices, systems and methods bywhich the blood pressure, nervous system activity, and neurohormonalactivity may be selectively and controllably regulated by activatingbaroreceptors or by inhibiting/dampening baroreceptor signals. Thus, thepresent invention may be used to increase or decrease blood pressure,sympathetic nervous system activity and neurohormonal activity, asneeded to minimize deleterious effects on the heart, vasculature andother organs and tissues.

The baroreceptor activation devices described previously may also beused to provide antiarrhythmic effects. It is well known that thesusceptibility of the myocardium to the development of conductiondisturbances and malignant cardiac arrhythmias is influenced by thebalance between sympathetic and parasympathetic nervous systemstimulation to the heart. That is, heightened sympathetic nervous systemactivation, coupled with decreased parasympathetic stimulation,increases the irritability of the myocardium and likelihood of anarrhythmia. Thus, by decreasing the level of sympathetic nervous systemactivation and enhancing the level of parasympathetic activation, thedevices, systems and methods of the current invention may be used toprovide a protective effect against the development of cardiacconduction disturbances.

In most activation device embodiments described herein, it may bedesirable to incorporate anti-inflammatory agents (e.g., steroid elutingelectrodes) such as described in U.S. Pat. No. 4,711,251 to Stokes, U.S.Pat. No. 5,522,874 to Gates and U.S. Pat. No. 4,972,848 to Di Domenicoet al., the entire disclosures of which are incorporated herein byreference. Such agents reduce tissue inflammation at the chronicinterface between the device (e.g., electrodes) and the vascular walltissue, to thereby increase the efficiency of stimulus transfer, reducepower consumption, and maintain activation efficiency, for example.

Those skilled in the art will recognize that the present invention maybe manifested in a variety of forms other than the specific embodimentsdescribed and contemplated herein. Accordingly, departures in form anddetail may be made without departing from the scope and spirit of thepresent invention as described in the appended claims.

The invention claimed is:
 1. A baroreflex modification system comprising: a baroreceptor activation device arranged to be coupled to a vascular wall, the vascular wall containing at least one baroreceptor; and a control system comprising a driver coupled to the baroreceptor activation device, the driver being configured to drive mechanical motion of at least a portion of the activation device, wherein the mechanical motion causes indirect activation of the baroreceptor by stretching or deforming the vascular wall surrounding the baroreceptor.
 2. The system of claim 1, wherein the control system includes a processor and a programmable memory, the control system programmed to generate a control signal and deliver the control signal to the driver.
 3. The system of claim 2, comprising a user interface coupled to the control system, the user interface being arranged to receive a value or a command in relation to the generated control signal, wherein the memory is configured to store data related to the generated control signal and/or the value or command received by the user interface.
 4. The system of claim 2, wherein the memory stores a stimulus regimen, wherein the control system is arranged to generate the control signal in accordance with the stimulus regimen.
 5. The system of claim 4, wherein the stimulus regimen is chosen to promote long term efficacy of baroreceptor activation.
 6. The system of claim 4, wherein the stimulus regimen comprises a first level to establish a desired therapeutic effect and a second level to sustain the desired effect.
 7. The system of claim 2, wherein the control signal comprises a continuous, periodic or episodic signal, or a combination thereof.
 8. The system of claim 7, wherein an episodic control signal can be triggered by an episode wherein the episode comprises a sensed increase of a physiological parameter above a certain threshold and/or a sensed decrease below of a physiological parameter below a certain threshold.
 9. The system of claim 1, wherein the activation device is arranged for pneumatic or hydraulic actuation in response to the control signal so as to compress and/or expand the tissue.
 10. The system of claim 1, comprising a sensor coupled to the control system, wherein the sensor is configured to monitor a parameter indicative of a need to modify the baroreflex system and to provide to the control system a sensor signal indicative of the sensed parameter.
 11. The system of claim 10, wherein the control system contains software containing an algorithm defining one or more functions or relationships between the control signal and the sensor signal, wherein the algorithm prescribes starting or stopping provision of the control signal to the driver based on the sensor signal.
 12. The system of claim 11, wherein the algorithm dictates one or more of the following starting or stopping provision of the control signal when the sensor signal falls below a predetermined threshold value or rises above a predetermined threshold value or when the sensor signal indicates a specific physiological event.
 13. The system of claim 1, wherein the baroreceptor activation device comprises an intravascular device.
 14. The system of claim 13, wherein the activation device comprises an intravascular inflatable balloon having a geometry which allows blood perfusion therethrough.
 15. The system of claim 14, wherein the driver comprises an inflation device in fluid communication with a fluid reservoir, the driver being coupled to the activation device by at least one fluid line.
 16. The system of claim 15, wherein the inflation device comprises a pressure or a vacuum source.
 17. The system of claim 14, wherein the intravascular inflatable balloon includes a helical geometry.
 18. The system of claim 13, wherein the activation device comprises an intravascular mechanical expansion device having tubular braid configured to diametrically expand when longitudinally compressed.
 19. The system of claim 13, wherein the activation device comprises an intravascular flow regulator arranged to artificially create back pressure adjacent the baroreceptor, the intravascular flow regulator comprising a valve configured to at least partially close the vascular lumen.
 20. The system of claim 1, wherein the baroreceptor activation device comprises an extravascular device.
 21. The system of claim 20, wherein the activation device comprises an extravascular inflatable pressure cuff.
 22. The system of claim 21, wherein the driver comprises an inflation device in fluid communication with a fluid reservoir, the driver being coupled to the activation device by at least one fluid line, optionally wherein the inflation device comprises a pressure or a vacuum source.
 23. The system of claim 22, wherein the inflation device comprises a pressure or a vacuum source.
 24. The system of claim 20, wherein the activation device comprises an extravascular mechanical compression device, wherein the compression device comprises a piston device, the piston device being actuated by solenoid, hydraulic or pneumatic means.
 25. The system of claim 24, wherein the activation device comprises an extravascular mechanical compression device, wherein the compression device comprises a rotary ring compression device.
 26. The system of claim 20, wherein the activation device comprises an extravascular flow regulator arranged to artificially create back pressure adjacent the baroreceptor, the extravascular flow regulator comprising an external compression device.
 27. The system of claim 1, wherein the activation device comprises a transducer, wherein the driver is an electric power generator or amplifier and is coupled to the activation device by at least one electrical lead, wherein the transducer comprises an acoustic transmitter arranged to transmit sonic or ultrasonic waves into vascular wall to cause vibration of the vascular wall.
 28. The system of claim 1, wherein the activation device is configured to be implanted at a location within a patient proximate one or more baroreceptors, the location selected from the group consisting of: a carotid sinus, an aortic arch, a common carotid artery, a subclavian artery, a brachiocephalic artery, and a heart.
 29. An implantable baroreflex modification system, comprising: a baroreceptor activation device arranged to be coupled to a vascular wall, the vascular wall containing at least one baroreceptor, wherein the activation device includes a means for mechanically activating the baroreceptor; and a control system coupled to the baroreceptor activation device, the control system programmed to deliver a control signal to the baroreceptor activation device to cause the means for mechanically activating to stretch or deform the vascular wall surrounding the baroreceptor.
 30. A method, comprising: causing a baroreceptor activation device to be manufactured and made available to a user; causing a control system to be manufactured and made available to the user, the control system comprising a driver coupled to the baroreceptor activation device; and providing instructions to the user, comprising: implanting the baroreceptor activation device in contact with a vascular wall, the vascular wall containing at least one baroreceptor; and causing the driver to drive mechanical motion of at least a portion of the activation device, wherein the mechanical motion causes indirect activation of the baroreceptor by stretching or deforming the vascular wall surrounding the baroreceptor. 